Abstract Thegoalofthisresearchistoidentifythemechanismsbywhicheccrineglandsareformedwith theultimateaimofregeneratingeccrineglandsindamagedhumanskinorinvitrogenerated skingrafts.WehavedevelopedatransgenicmouselinethatallowsinducibleexpressionofEn1 intheepidermisandhaveshownthatinductionofEn1duringanarrowtimewindow surroundingtheinitiationofcutaneousappendagedevelopmentintheregionbetweenthe footpadsofanewbornmouseissufficienttoachieveacompletehomeoticconversionof cutaneousappendages,normallyhairfolliclesinthisregion,toeccrinesweatglands.Wewill exploitthismousetoidentifythegeneticpathwaysthatspecifyeccrineglanddevelopment insteadofhairfollicleformationfromacommonepidermalplacode.TheeffectsofforcedEn1 expressiononinductivesignalingfromthedermisandongeneexpressionintheepidermis beforeandafterplacodeinductionwillbecharacterized.ChIPmentationwillbeusedtoidentify thesubsetofthesegenesthataredirectlyregulatedbyEn1andproximalmediatorsofthis effect.Theoutcomeofthisresearchwillincludetheidentificationofthegeneticpathwaysthat specifythedistinctivedevelopmentalpathoftheeccrineglandplacodeandthedermalsignals thatinitiatethisprocess.TheapproachalsoteststwoalternativemodelsofEn1action.Ifoneof thesealternativesissupported,itwillbeaparadigm-shiftingoutcomethatemphasizestherole oftheepidermisinappendagefatechoice.Iftheotherissupported,itwillnonethelessadvance thefieldbyhelpingtoidentifytheuniquecomponentsoftheinductivesignalfromthedermis thatdriveEGdevelopment.