@entity5018 slows migration and inhibits bowel colonization by enteric nervous system precursors in @entity3392 , XXXX and @entity19 .

@entity1 @entity16538 @entity10178 @entity48901 @entity19 @entity5018 @entity11120 @entity1963 @entity7517 @entity600 @entity1573 @entity5844 @entity1996 @entity3392
UNASSIGNED: @entity1963 ( @entity1963 ) is a potentially deadly @entity600 characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although @entity1963 has clear genetic causes, no @entity1963 -associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine @entity1963 occurrence. To test the hypothesis that certain medicines might alter @entity1963 risk we treated @entity3392 with medications commonly used during early @entity1 pregnancy and discovered that @entity5018 caused @entity1963 -like absence of enteric neurons in distal bowel. Using fetal CF-1 @entity19 gut slice cultures, we found that @entity5018 treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active @entity5844 / @entity11120 . Additionally, inhibiting ROCK, a RHOA effector and known @entity5844 antagonist, reversed @entity5018 effects on migrating @entity19 ENCDC in culture. @entity5018 also inhibited colonization of @entity7517 +/- @entity19 bowel by ENCDC in vivo and dramatically reduced bowel colonization by @entity1573 ENCDC in culture. Interestingly, @entity5018 did not affect ENCDC migration until after at least three hours of exposure. Furthermore, @entity19 deficient in @entity48901 ( @entity16538 ) and @entity1996 ( @entity10178 ) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, @entity5018 did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in @entity3392 . Thus, @entity5018 inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in @entity3392 , @entity19 and @entity1573 , but there are cell type and strain specific responses. These data raise concern that @entity5018 may increase @entity1963 risk in some genetically susceptible @entity1 .
