Ectoderm-Mesenchyme and Mesenchyme-Mesenchyme Interactions Regulate Msx-1 Expression and Cellular Differentiation in the Murine Limb Bud

摘要

Theapicalectodermalridge(AER)isaspecializedthickeningofthedistallimbmesenchymethathasbeendemonstratedtosupportlimboutgrowthandproperlimbdevelopment.Thehomeoboxgene,Max-1,isassociatedwiththedistallimbmesenchyme(progresszone)anditsexpressiondependsuponthepresenceoftheAERinchicklimbs.WedemonstrateherethattheexpressionofMax-1isdependentuponthelimbectoderminthemouse,butthattheinductivecapacityofmurinelimbectodermisnotrestrictedtotheAER.Msx-1canalsohemaintainedinlimbmesenchymebythesubstitutionofFGF4fortheectoderm;however,weseethatlocalcell-cellinteractionsarerequiredforhighlevelsofexpression.Disruptionofcell-callinteractionsinthelimbmesenchymeresultsinadramaticdecreaseinMsx-1levelsandaprecociousexpressionofMyoD1,suggestingthatthelimbenvironmentrepressesdifferentiationandpromotescellproliferationduringearlydevelopment.BMP4andFGF2canalsomaintainMsx-1expressioninlimbmesenchymeaswellasretinoicacidwhichisusuallyassociatedwithpolarizingactivityintheearlylimb.Max-2expressiondoesnotappeartobedependentuponcell-cellinteractionsasmeasuredintheseexperiments.Takentogether,ourdatasuggestthattheexpressionofMax-1,butnotMax-2,notonlyrequiresfactorsfromthelimbectoderm,butalsoreliesuponcuesfromlocalcellinteractionsandthatthespatialdistributionofinductivecapacitiesinlimbectodermdiffersbetweentheavianandmurinesystems./p/div