Associate ProfessorOffice: Anatomy/Zoology Building E328APhone: 970-491-2513Education: Ph.D., Cornell UniversityEmail: Deborah.Garrity@ColoState.EDU
The development of the embryonic heart involves cell specification and differentiation, tissue patterning and morphogenetic movements. What genes are required for these processes and what are their specific roles? To address this question, we identified over 60 mutants that disrupt early organ development in a large-scale screen. The embryonic lethal tremblor (tre) mutant exhibits cardiac arrhythmia from onset of cardiac contraction. We identified a premature stop codon in a cardiac-specific Na+/Ca2+ exchanger gene (NCX1h) as the cause of the tremblor phenotype. Calcium overload appears to contribute to the degeneration of cardiac function in this mutant.
We have recently begun to study the spectacular cell movements of early embryo morphogenesis, readily visible in transparent zebrafish embryos. In early stages, the embryo consists of a mound of cells positioned over a large yolk mass. During 'epiboly', the cell mass begins to spread and thin, eventually surrounding the entire yolk. Though first described over 170 years ago, relatively little is known about the cell biology that underlies the control of these movements. The question is significant because epiboly and later stages of gastrulation are fundamental to the establishment of the germ layers from which all subsequent organs derive. We found that two calcium channel beta subunit (CACNB4) genes are essential for epiboly. Surprisingly, the ability of CACNB4 proteins to assemble with calcium channels turns out to be irrelevant for its function in epiboly. Instead, we are investigating the possibility that the CACNB4 proteins have a scaffolding function, consistent with their protein structure.
Rothschild SC, Easley CA, Francescatto L, Lister JA, Garrity DM, Tombes RM. Tbx5-mediated expression of Ca2+/calmodulin-dependentprotein kinase II is necessary for zebrafish cardiac and pectoral fin development. Developmental Biology, April 1 (2009) [Epub ahead of print].
Ebert AM, McAnelly CA, Handschy A, Mueller RL, Horne WA and Garrity DM. Genomic organization, expression and phylogenetic analysis of Ca2+ channel β4 (CACNB4) genes in thirteen vertebrate species. Physiological Genomics 2008 Aug 5.
Ebert AM, McAnelly CA, Srinivasan A, Mueller RL, Garrity DB and Garrity DM. The calcium channel β2 (CACNB2) subunit repertoire in teleosts. BMC Molecular Biology, 9:38 (2008).
Qu X, Jia H, Garrity DM, Tompkins K, Batts L, Appel B, Zhong T, Baldwin SH. ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. 15;317(2):486-96(2008).
Ebert AM, McAnelly CA, Srinivasan A, Linker JL, Horne WA and Garrity DM. Ca2+ channel-independent requirement for MAGUK-family CACNB4 genes in initiation of zebrafish epiboly. Proc. Natl. Acad. Sci. U.S.A. 105 (1), 198-203 (2008)
Ebert AM, Hume GL, Warren KS, Cook NP, Burns CG, Mohideen MA, Siegal G, Yelon D, Fishman MC, Garrity DM. Calcium extrusion is critical for cardiac morphogenesis and rhythmicity in embryonic zebrafish hearts. PNAS 102:17705-17710 (2005).
Garrity DM, Childs S, and Fishman MC. 2002. Heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome. Development 129:4635-4645.
Childs S, Chen JN, Garrity DM, and Fishman MC. 2002. Patterning of angiogenesis in the zebrafish embryo. Development 129:973-982.
Roman BL, Pham VN, Lawson ND , Kulik M, Childs S, Lekven AC, Garrity DM, Moon RT, Fishman MC, Lechleider RJ, and Weinstein BM. 2002. Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. Development 129:3009-3019.
Chen JN, van Bebber F, Goldstein AM, Serluca FC, Jackson D, Childs S, Serbedzija G, Warren KS, Mably JD, Garrity DM, Lindahl P, Mayer A, Haffter P, and Fishman MC. 2001. Genetic steps to organ laterality in zebrafish. Comp Funct Genom 2: 60-68.