Loss of the Sall3 Gene Leads to Palate Deficiency, Abnormalities in Cranial Nerves, and Perinatal Lethality

Abstract

Members of the Spalt gene family encode putative transcription factors characterized by seven to nine C2H2 zinc finger motifs. Four genes have been identified in mice—Spalt1 to Spalt4 (Sall1 to Sall4). Spalt homologues are widely expressed in neural and mesodermal tissues during early embryogenesis. Sall3 is normally expressed in mice from embryonic day 7 (E7) in the neural ectoderm and primitive streak and subsequently in the brain, peripheral nerves, spinal cord, limb buds, palate, heart, and otic vesicles. We have generated a targeted disruption of Sall3 in mice. Homozygous mutant animals die on the first postnatal day and fail to feed. Examination of the oral structures of these animals revealed that abnormalities were present in the palate and epiglottis from E16.5. In E10.5 embryos, deficiencies in cranial nerves that normally innervate oral structures, particularly the glossopharyngeal nerve (IX), were observed. These studies indicate that Sall3 is required for the development of nerves that are derived from the hindbrain and for the formation of adjacent branchial arch derivatives.

We thank Dagmar Bock, Kristin Bond, Emily Sours, and Kirsten Boyer-Mauro for excellent technical assistance. We are grateful to Kathleen Kuznicki for commenting on the manuscript. We thank the following people for providing probes: Marsha Ontell (myogenic regulatory factors) and Andy McMahon (Shh).

This study was supported by NIMH grant no. 5RO1MH060774-03, MOD Basil O'Connor grant no. S-FY98-756, and NIH grant no. T32 MH18273.