Jeffrey Hildebrand

  • Associate Professor
  • Cell morphology

Contact

Office: (412) 624-6987
Lab: (412) 624-6987
103A Life Sciences Annex
4249 Fifth Avenue
Pittsburgh, PA 15260

How is it that cells manage to regulate their shape and organization during embryonic development in order to form the various tissues and diverse body plans seen in adult organisms? In most circumstances, cells utilize the coordinated efforts of signaling pathways, effector proteins, cytoskeletal networks, and contractile myosins to elicit the changes in cell morphology needed toform tissues and structures with beautiful and elaborate architecture.  Understanding the regulation and integration of these cellular components, pathways, and networks in these fascinating processes is the main objective of the work in the Hildebrand lab.  We use a variety of genetic, cellular, biochemical, molecular, and structural approaches to understand how cell and tissue morphology is regulated.  We are currently studying the function and regulation of the Shroom family of proteins as a model to understand these processes. 

Figure 1.  Wildtype E8.5 mouse embryo was stained to detect Shroom3 (green) and F-actin (red).  The neural plate was then imaged via confocal microscopy.

Using numerous in vivo and in vitro model systems and approaches, we have shown that Shroom proteins are a family of actin-associated scaffolding molecules that control cellular architecture and tissue morphology during processes such as neural tube closure (Figure 1), kidney formation (Figure 2), and Drosophila embryogenesis. To date we have characterized the functions of vertebrate Shroom2, 3, and 4 and the ortholog of Shroom, from Drosophila melanogaster.  It appears that all Shroom proteins control cell and tissue architecture by regulating the distribution of contractile actomyosin networks.  This activity is dependent on the ability of Shroom proteins to bind and recruit Rho-kinase, an activator of non-muscle myosin II, to specific regions of the cell.  Once recruited, we hypothesize that Rock locally activates myosin II and subsequently changes or regulates cell contractility or shape. The current work in our lab endeavors to understand the molecular, biochemical, and cellular basis for how Shroom proteins control actomyosin networks.  In addition, we are trying to elucidate how different types of contractile networks are assembled in a cell and what outcomes these different types of networks may have on cell behavior and tissue morphology.  Finally, we are using cellular and genetic analysis to define other players in the Shroom network and identify other pathways that cooperate with Shroom to control cellular behaviors. 

Figure 2. Sections from a wildtype E18.5 kidney was stained to detect Shroom3 (green), F-actin (red), and DNA (blue) and visualized by confocal microscopy.

E-mail Lab

Grego-Bessa J, Hildebrand JD, Anderson KV (2015

Grego-Bessa J, Hildebrand JD, Anderson KV (2015) Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains. Development. 42(7):1305-14

McGreevy EM, Vijayraghavan D, Davidson LA, Hild

McGreevy EM, Vijayraghavan D, Davidson LA, Hildebrand JD. (2015) Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure. Biol Open. doi: 10.1242/​bio.20149589

Das D, Zalewski JK, Mohan S, Plageman TF, VanDe

Das D, Zalewski JK, Mohan S, Plageman TF, VanDemark AP, Hildebrand JD. (2014) The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice. Biol Open. 3(9):850-60

Lang RA, Herman K, Reynolds AB, Hildebrand JD,

Lang RA, Herman K, Reynolds AB, Hildebrand JD, Plageman TF Jr. (2014) p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis. Development. 141(16):3177-87.

Mohan, S., Das, D., Bauer, RJ, Heroux, A., Zale

Mohan, S., Das, D., Bauer, RJ, Heroux, A., Zalewski, J.K., Heber, S., Dosunmu-Ogunbi, A.M., Trakselis, M.A., Hildebrand, J.D., VanDemark, A,P. (2013) Structure of a highly conserved domain of Rock1 required for Shroom-mediated regulation of cell morphology. PLoS One 8(12):e81075

Mohan S, Rizaldy R, Das D, Bauer RJ, Heroux A,

Mohan S, Rizaldy R, Das D, Bauer RJ, Heroux A, Trakselis MA, Hildebrand JD, VanDemark AP (2012) Structure of the Shroom Domain 2 reveals a three-segmented coiled-coil required for dimerization, Rock binding, and apical constriction. . Mol Biol Cell. 22:795-805    PMCID: PMC3364177

Plageman TF Jr, Chauhan BK, Yang C, Jaudon F, Shang X, Zheng Y, Lou M, Debant A, Hildebrand JD, L

Plageman TF Jr, Chauhan BK, Yang C, Jaudon F, Shang X, Zheng Y, Lou M, Debant A, Hildebrand JD, Lang RA. (2011) A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination. Development. 138:5177-88

Grosse AS, Pressprich MF, Curley LB, Hamilton KL, Margolis B, Hildebrand JD, Gumucio DL. (2011) C

Grosse AS, Pressprich MF, Curley LB, Hamilton KL, Margolis B, Hildebrand JD, Gumucio DL. (2011) Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis. Development.138 (20): 4423-32.

Farber, M.J., R. Rizaldy, and J.D. Hildebrand (2011) Shroom2 regulates contractility to control e

Farber, M.J., R. Rizaldy, and J.D. Hildebrand (2011) Shroom2 regulates contractility to control endothelial morphogenesis. Mol Biol Cell 22:795-805

Mo, D., B.A. Potter, C.A. Bertrand, J.D. Hildebrand, J.R. Bruns, and O.A. Weisz (2010) Nucleofect

Mo, D., B.A. Potter, C.A. Bertrand, J.D. Hildebrand, J.R. Bruns, and O.A. Weisz (2010) Nucleofection disrupts tight junction fence function to alter membrane polarity of renal epithelial cells. Am. J. Physiol. Renal Physiol. 299(5):F1178-84

Bolinger, C., L. Zasadil, R. Rizaldy, and J.D. Hildebrand (2010) Specific isoforms of Drosoph

Bolinger, C., L. Zasadil, R. Rizaldy, and J.D. Hildebrand (2010) Specific isoforms of Drosophila shroom define spatial requirements for the induction of apical constriction. Dev. Dynam. 239:2078-2093

Plageman TF, J.r, M.I. Chung, M. Lou, A.N. Smith, J.D. Hildebrand, J.B. Wallingford, and R.A. Lan

Plageman TF, J.r, M.I. Chung, M. Lou, A.N. Smith, J.D. Hildebrand, J.B. Wallingford, and R.A. Lang (2010) Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development 137:405-415

Yoder, M., and J.D. Hildebrand (2007) Shroom4 (KIAA1202) is an actin-associated protein implicate

Yoder, M., and J.D. Hildebrand (2007) Shroom4 (KIAA1202) is an actin-associated protein implicated in cytoskeletal organization. Cell Motil. Cytoskel. 64:49-63

Hagens, O., A. Ballabio, V. Kalscheuer, J.P. Kraehenbuhl, M.V. Schiaffino, P. Smith, O. Staub, J.

Hagens, O., A. Ballabio, V. Kalscheuer, J.P. Kraehenbuhl, M.V. Schiaffino, P. Smith, O. Staub, J. Hildebrand, and J.B. Wallingford (2006) A new standard nomenclature for proteins related to Apx and Shroom. BMC Cell Biol 7:18

Fairbank, P.D., C. Lee, A. Ellis, J.D. Hildebrand, J.M. Gross, and J.B. Wallingford (2006) Shroom

Fairbank, P.D., C. Lee, A. Ellis, J.D. Hildebrand, J.M. Gross, and J.B. Wallingford (2006) Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium. Development 133:4109-4118

Dietz, M.L., T.M. Bernaciak, F. Vendetti, and J.D. Hildebrand (2006) Differential actin-dependent

Dietz, M.L., T.M. Bernaciak, F. Vendetti, and J.D. Hildebrand (2006) Differential actin-dependent localization modultes the evolutionarily conserved activity of shroom-family proteins. J. Biol. Chem. 281:20542-20554

Hildebrand, J.D. (2005) CtBP proteins in vertebrate development. Pp in CtBP Family Proteins

Hildebrand, J.D. (2005) CtBP proteins in vertebrate development. Pp in CtBP Family Proteins, Chinnadurai, G., Ed. Landes Bioscience

Hildebrand, J.D. (2005) Shroom regulates epithelial cell shape via the apical positioning of an a

Hildebrand, J.D. (2005) Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J. Cell Sci. 118:5191-5203

Haigo, S.L., J.D. Hildebrand, R.M. Harland, and J.B. Wallingford (2003) Shroom induces apical con

Haigo, S.L., J.D. Hildebrand, R.M. Harland, and J.B. Wallingford (2003) Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr. Biol. 13:2125-2137

Zhang, Q., Y. Yoshimatsu, J. Hildebrand, S.M. Frisch, and R.H. Goodman (2003) Homeodomain Interac

Zhang, Q., Y. Yoshimatsu, J. Hildebrand, S.M. Frisch, and R.H. Goodman (2003) Homeodomain Interacting Protein Kinase 2 Promotes Apoptosis by Downregulating the Transcriptional Corepressor CtBP. Cell 115:177-186

Lin, X., B. Sun, M. Liang, Y.Y. Liang, A. Gast, J. Hildebrand, F.C. Brunicardi, F. Melchior, and

Lin, X., B. Sun, M. Liang, Y.Y. Liang, A. Gast, J. Hildebrand, F.C. Brunicardi, F. Melchior, and X.H. Feng (2003) Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol. Cell 11:1389-1396

Grooteclaes, M., Q. Deveraux, J. Hildebrand, Q. Zhang, R.H. Goodman, and S.M. Frisch (2003) C-ter

Grooteclaes, M., Q. Deveraux, J. Hildebrand, Q. Zhang, R.H. Goodman, and S.M. Frisch (2003) C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc. Natl. Acad. Sci., USA 100:4568-4573

Hildebrand, J.D., and P. Soriano (2002) Overlapping and unique roles for C-terminal binding prote

Hildebrand, J.D., and P. Soriano (2002) Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol. Cell. Biol. 22:5296-5307
Dr. Hildebrand received his Ph.D. in 1995 with J. Thomas Parsons at the University of Virginia, performed his postdoctoral studies with Philippe Soriano at the Fred Hutchinson Cancer Research Center, and joined the Department in 2000.