Jeremy Reiter, MD, PhD

Director, Developmental & Stem Cell Biology Program
Professor
Department of Biochemistry and Biophysics
+1 415 502-8528

Eukaryotic cilia and flagella are cellular structures familiar to schoolchildren everywhere for the elegant swath they cut as they propel protozoa through pond water. Less well recognized is the fact that a single immotile cilium is present on almost every type of vertebrate cell. These so-called primary cilia were discovered more than a century ago and, yet, their functions remain largely unexplored (Singla and Reiter, 2006).

It is now becoming clear that the primary cilium plays important roles in both development and disease. Perhaps its most dramatic function is in the kidney - ciliary defects cause polycystic kidney disease, the most common life-threatening monogenic illness. Primary cilia also have roles in sensing environmental information. Photoreceptors and odorant receptors function on primary cilia, and primary cilia are essential for sound reception. Therefore, it is not much of an exaggeration to say that we see, smell and hear through cilia.

Our work suggests that cilia also function as critical mediators of intercellular signals during development (Corbit et al., 2005; May et al., 2005; Reiter and Skarnes, 2006). One crucial role is in the coordination of the Hedgehog signal transduction pathway. Hedgehog signals are essential regulators of embryonic patterning and cell proliferation, and defects in Hedgehog signaling are important causes of both birth defects and many cancers. We are currently extending this work by asking a few fundamental questions about primary cilia:

  • Do cilia transduce intercellular signals other than Hedgehog?
  • How do cilia interpret signals essential to vertebrate development?
  • Do cilia participate in Hedgehog-mediated oncogenesis?
  • How do cells regulate whether they form a cilium?

This work has begun to suggest that the primary cilium is an organelle dedicated to signal transduction, somewhat analogous to a cellular antenna. We hope that our current endeavors will reveal how this antenna interprets the signals required for normal development and homeostasis, and how malfunctions in the antenna contribute to cancer and other important human diseases.

Research Summary: 
Signaling at the Primary Cilium, the Cell's Antenna
Publications: 

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Nature genetics

Siljee JE, Wang Y, Bernard AA, Ersoy BA, Zhang S, Marley A, Von Zastrow M, Reiter JF, Vaisse C

Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.

Developmental cell

Sigg MA, Menchen T, Lee C, Johnson J, Jungnickel MK, Choksi SP, Garcia G, Busengdal H, Dougherty GW, Pennekamp P, Werner C, Rentzsch F, Florman HM, Krogan N, Wallingford JB, Omran H, Reiter JF

Hedgehog signaling drives medulloblastoma growth via CDK6.

The Journal of clinical investigation

Raleigh DR, Choksi PK, Krup AL, Mayer W, Santos N, Reiter JF

Erratum: Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome.

Nature cell biology

Shi X, Garcia G, Van De Weghe JC, McGorty R, Pazour GJ, Doherty D, Huang B, Reiter JF

Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome.

Nature cell biology

Shi X, Garcia Iii G, Van De Weghe JC, McGorty R, Pazour GJ, Doherty D, Huang B, Reiter JF

Genes and molecular pathways underpinning ciliopathies.

Nature reviews. Molecular cell biology

Reiter JF, Leroux MR

Cilia and Obesity.

Cold Spring Harbor perspectives in biology

Vaisse C, Reiter JF, Berbari NF

Open Sesame: How Transition Fibers and the Transition Zone Control Ciliary Composition.

Cold Spring Harbor perspectives in biology

Garcia-Gonzalo FR, Reiter JF

Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision.

Cell

Phua SC, Chiba S, Suzuki M, Su E, Roberson EC, Pusapati GV, Setou M, Rohatgi R, Reiter JF, Ikegami K, Inoue T

Microcephaly Proteins Wdr62 and Aspm Define a Mother Centriole Complex Regulating Centriole Biogenesis, Apical Complex, and Cell Fate.

Neuron

Jayaraman D, Kodani A, Gonzalez DM, Mancias JD, Mochida GH, Vagnoni C, Johnson J, Krogan N, Harper JW, Reiter JF, Yu TW, Bae BI, Walsh CA

Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex.

Cell

Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA

A primer on the mouse basal body.

Cilia

Garcia G, Reiter JF

MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.

PLoS biology

Li C, Jensen VL, Park K, Kennedy J, Garcia-Gonzalo FR, Romani M, De Mori R, Bruel AL, Gaillard D, Doray B, Lopez E, Rivière JB, Faivre L, Thauvin-Robinet C, Reiter JF, Blacque OE, Valente EM, Leroux MR

Endothelial primary cilia inhibit atherosclerosis.

EMBO reports

Dinsmore C, Reiter JF

Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling.

PLoS genetics

Yee LE, Garcia-Gonzalo FR, Bowie RV, Li C, Kennedy JK, Ashrafi K, Blacque OE, Leroux MR, Reiter JF

Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog Signaling.

Developmental cell

Garcia-Gonzalo FR, Phua SC, Roberson EC, Garcia G, Abedin M, Schurmans S, Inoue T, Reiter JF

Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.

eLife

Kodani A, Yu TW, Johnson JR, Jayaraman D, Johnson TL, Al-Gazali L, Sztriha L, Partlow JN, Kim H, Krup AL, Dammermann A, Krogan NJ, Walsh CA, Reiter JF

TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone.

The Journal of cell biology

Roberson EC, Dowdle WE, Ozanturk A, Garcia-Gonzalo FR, Li C, Halbritter J, Elkhartoufi N, Porath JD, Cope H, Ashley-Koch A, Gregory S, Thomas S, Sayer JA, Saunier S, Otto EA, Katsanis N, Davis EE, Attié-Bitach T, Hildebrandt F, Leroux MR, Reiter JF

Ciliary vesicle formation: a prelude to ciliogenesis.

Developmental cell

Yee LE, Reiter JF

Katanin p80 regulates human cortical development by limiting centriole and cilia number.

Neuron

Hu WF, Pomp O, Ben-Omran T, Kodani A, Henke K, Mochida GH, Yu TW, Woodworth MB, Bonnard C, Raj GS, Tan TT, Hamamy H, Masri A, Shboul M, Al Saffar M, Partlow JN, Al-Dosari M, Alazami A, Alowain M, Alkuraya FS, Reiter JF, Harris MP, Reversade B, Walsh CA

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.

Proceedings of the National Academy of Sciences of the United States of America

Ye X, Zeng H, Ning G, Reiter JF, Liu A

Hedgehog signaling controls T cell killing at the immunological synapse.

Science (New York, N.Y.)

de la Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH, Reiter JF, Griffiths GM

Keratin 79 identifies a novel population of migratory epithelial cells that initiates hair canal morphogenesis and regeneration.

Development (Cambridge, England)

Veniaminova NA, Vagnozzi AN, Kopinke D, Do TT, Murtaugh LC, Maillard I, Dlugosz AA, Reiter JF, Wong SY

Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism.

Journal of molecular endocrinology

D'Amico E, Gayral S, Massart C, Van Sande J, Reiter JF, Dumont JE, Robaye B, Schurmans S

Kif3a interacts with Dynactin subunit p150 Glued to organize centriole subdistal appendages.

The EMBO journal

Kodani A, Salomé Sirerol-Piquer M, Seol A, Garcia-Verdugo JM, Reiter JF

Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.

Proceedings of the National Academy of Sciences of the United States of America

Wu VM, Chen SC, Arkin MR, Reiter JF

Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access.

The Journal of cell biology

Garcia-Gonzalo FR, Reiter JF

A high-fat diet regulates gastrin and acid secretion through primary cilia.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Saqui-Salces M, Dowdle WE, Reiter JF, Merchant JL

Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.

PLoS genetics

Hunkapiller J, Shen Y, Diaz A, Cagney G, McCleary D, Ramalho-Santos M, Krogan N, Ren B, Song JS, Reiter JF

Disruption of a ciliary B9 protein complex causes Meckel syndrome.

American journal of human genetics

Dowdle WE, Robinson JF, Kneist A, Sirerol-Piquer MS, Frints SG, Corbit KC, Zaghloul NA, Zaghloul NA, van Lijnschoten G, Mulders L, Verver DE, Zerres K, Reed RR, Attié-Bitach T, Johnson CA, García-Verdugo JM, Katsanis N, Bergmann C, Reiter JF

A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.

Nature genetics

Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, García-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF

Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways.

Cell

Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Sfakianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, O'Toole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi AR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F, Reiter JF, Jackson PK

Role of epidermal primary cilia in the homeostasis of skin and hair follicles.

Development (Cambridge, England)

Croyle MJ, Lehman JM, O'Connor AK, Wong SY, Malarkey EB, Iribarne D, Dowdle WE, Schoeb TR, Verney ZM, Athar M, Michaud EJ, Reiter JF, Yoder BK

Wounding mobilizes hair follicle stem cells to form tumors.

Proceedings of the National Academy of Sciences of the United States of America

Wong SY, Reiter JF

Crippling SWI-SNF makes tumors GLI-ful.

Nature medicine

Reiter JF

Vive la science! Vive le hérisson!

EMBO reports

Reiter JF, de Sauvage FJ

Ofd1, a human disease gene, regulates the length and distal structure of centrioles.

Developmental cell

Singla V, Romaguera-Ros M, Garcia-Verdugo JM, Reiter JF

Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation.

Cell stem cell

Walker E, Chang WY, Hunkapiller J, Cagney G, Garcha K, Torchia J, Krogan NJ, Reiter JF, Stanford WL

Floxin, a resource for genetically engineering mouse ESCs.

Nature methods

Singla V, Hunkapiller J, Santos N, Seol AD, Norman AR, Wakenight P, Skarnes WC, Reiter JF

Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis.

Nature medicine

Wong SY, Seol AD, So PL, Ermilov AN, Bichakjian CK, Epstein EH, Dlugosz AA, Reiter JF

The extracellular domain of Smoothened regulates ciliary localization and is required for high-level Hh signaling.

Current biology : CB

Aanstad P, Santos N, Corbit KC, Scherz PJ, Trinh le A, Salvenmoser W, Huisken J, Reiter JF, Stainier DY

Building it up and taking it down: the regulation of vertebrate ciliogenesis.

Developmental dynamics : an official publication of the American Association of Anatomists

Santos N, Reiter JF

The primary cilium at the crossroads of mammalian hedgehog signaling.

Current topics in developmental biology

Wong SY, Reiter JF

Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms.

Nature cell biology

Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH, Chuang PT, Reiter JF

Vesicle transport, cilium formation, and membrane specialization: the origins of a sensory organelle.

Proceedings of the National Academy of Sciences of the United States of America

Reiter JF, Mostov K

Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli.

Developmental biology

May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS

Vertebrate Smoothened functions at the primary cilium.

Nature

Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF

Notch signaling can regulate endoderm formation in zebrafish.

Developmental dynamics : an official publication of the American Association of Anatomists

Kikuchi Y, Verkade H, Reiter JF, Kim CH, Chitnis AB, Kuroiwa A, Stainier DY

Multiple roles for Gata5 in zebrafish endoderm formation.

Development (Cambridge, England)

Reiter JF, Kikuchi Y, Stainier DY

Gata5 is required for the development of the heart and endoderm in zebrafish.

Genes & development

Reiter JF, Alexander J, Rodaway A, Yelon D, Patient R, Holder N, Stainier DY

Glucagon immunoreactivities and amino acid profile in plasma of duodenopancreatectomized patients.

The Journal of clinical investigation

Muller WA, Berger M, Suter P, Cüppers HJ, Reiter J, Wyss T, Berchtold P, Schmidt FH, Assal JP, Renold AE