Danforth's short-tail (Sd) mouse is a semidominant mutation that prevents completion of notochord development. In homozygous mutant mice, the notochord completely degenerates at embryonic day 9.5 (E9.5), whereas the neural tube and somites continue to form, permitting analysis of somite development in the absence of inductive signals from the notochord and floor plate. In the somites formed after notochord degeneration, Myf5 expression initiates in a normal temporal sequence, but instead of the normal restriction to the dorsomedial somite, its expression extends into the ventral somite. MyoD, myogenin, and myosin heavy chain are normally expressed in the ventral myotome and there is normal development of hypaxial muscles. In contrast, subsequent to initial Myf5 expression, muscle gene expression was not detected in the dorsal myotome and a high level of apoptosis was observed with significantly decreased formation of epaxial muscles. The apoptosis of epaxial muscle in somites that formed after notochord degeneration is consistent with a role for the notochord in the survival and differentiation of the dorsal myotome.
Bibliographical noteFunding Information:
We thank Dr. Phillipe Soriano for Shh cDNA, Dr. Rudi Balling for Pax1 cDNA, Dr. Michael Rudnicki for Pax3 cDNA, and Dr. Jeff Miner for MRF4 gene. We are also grateful to Drs. Phillipe Soriano, Michael Rudnicki, and Boris Kablar for critical readings of the manuscript. This work was supported by the Muscular Dystrophy Association (MDA). A.A. was supported by a postdoctoral fellowship of the MDA.
- Danforth's short-tail
- Myogenic bHLH
- Sonic hedgehog
- Transgenic mice