Role of the homeodomain transcription factor Bapx1 in mouse distal stomach development.
OBJECTIVE
Expansion and patterning of the endoderm generate a highly ordered, multiorgan digestive system in vertebrate animals. Among distal foregut derivatives, the gastric corpus, antrum, pylorus, and duodenum are distinct structures with sharp boundaries. Some homeodomain transcription factors expressed in gut mesenchyme convey positional information required for anterior-posterior patterning of the digestive tract. Barx1, in particular, controls stomach differentiation and morphogenesis. The Nirenberg and Kim homeobox gene Bapx1 (Nkx3-2) has an established role in skeletal development, but its function in the mammalian gut is less clear.


METHODS
We generated a Bapx1(Cre) knock-in allele to fate map Bapx1-expressing cells and evaluate its function in gastrointestinal development.


RESULTS
Bapx1-expressing cells populate the gut mesenchyme with a rostral boundary in the hindstomach near the junction of the gastric corpus and antrum. Smooth muscle differentiation and distribution of early regional markers are ostensibly normal in Bapx1(Cre/Cre) gut, but there are distinctive morphologic abnormalities near this rostral Bapx1 domain: the antral segment of the stomach is markedly shortened, and the pyloric constriction is lost. Comparison of expression domains and examination of stomach phenotypes in single and compound Barx1 and Bapx1 mutant mice suggests a hierarchy between these 2 factors; Bapx1 expression is lost in the absence of Barx1.


CONCLUSIONS
This study reveals the nonredundant requirement for Bapx1 in distal stomach development, places it within a Barx1-dependent pathway, and illustrates the pervasive influence of gut mesenchyme homeobox genes on endoderm differentiation and digestive organogenesis.
Verzi
Michael P
MP
Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stanfel
Monique N
MN
Moses
Kelvin A
KA
Kim
Byeong-Moo
BM
Zhang
Yan
Y
Schwartz
Robert J
RJ
Shivdasani
Ramesh A
RA
Zimmer
Warren E
WE
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D011706:Pyloric Antrum / Q000002:abnormalities / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C095587:Barx1 protein, mouse; D018398:Homeodomain Proteins; C107965:Nkx3-2 protein, mouse; D014157:Transcription Factors