The molecular mechanisms underlying the specification of muscle pattern and the relationship of muscle pattern specification to skeletal and tendon pattern specification in the developing amniote limb are largely unknown. Myogenic precursor cells migrate into the limb and eventually differentiate into slow and fast myofibers arranged into 45 anatomical muscles. [To delineate when and where myogenic cells are being patterned, the fate of clonally-related myogenic cells will be analyzed by labeling myogenic precursors with CHAPOL replication defective retrovirus library.] lmx1 and hox transcription factors appear to be critical for specifying dorsal-ventral, anterior-posterior, and proximal-distal limb muscle pattern. The role of these genes in patterning particular phases of muscle morphogenesis will be assessed by retroviral misexpression of lmx1 and hoxd-11 in spatially inappropriate locations and at different times in the developing chick limb. Quail-chick chimeras and retroviral, tissue-specific manipulations of gene expression will determine how lmx1 and hoxd-11, initially expressed in the limb bud mesoderm, transmit their patterning information to muscle and provide an important means of dissecting the relationship between muscle, tendon, and skeleton morphogenesis during limb development. [In addition, novel genes involved in muscle patterning are being sought via a screen of a chick limb library for genes encoding secreted proteins].

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD008352-01A1
Application #
2771119
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Javois, Lorette Claire
Project Start
1999-07-19
Project End
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732
Birn, R M; Shackman, A J; Oler, J A et al. (2014) Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Mol Psychiatry 19:915-22
Shackman, Alexander J; Fox, Andrew S; Oler, Jonathan A et al. (2013) Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proc Natl Acad Sci U S A 110:6145-50