The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution of Wnts to the development of ventral midbrain (VM) dopaminergic (DA) neurons. Our results show that @entity12401 is expressed in DA precursor cells and that @entity12401 signaling takes place in these cells, as assessed in TOPGAL [Tcf optimal-promoter beta-galactosidase] reporter @entity19 . We also found that @entity6034 , -3a, and -5a expression is differentially regulated during development and that partially purified Wnts distinctively regulate VM development. @entity6035 promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 ( @entity55236 ) but did not increase the number of @entity669 hydroxylase-positive neurons. Instead, @entity68934 increased the number of @entity35 midbrain DA neurons in @entity35 embryonic day 14.5 precursor cultures by two distinct mechanisms. @entity6034 predominantly increased the proliferation of @entity55236 + precursors, up-regulated cyclins D1 and D3, and down-regulated @entity5447 and @entity25033 mRNAs. In contrast, @entity28407 primarily increased the proportion of @entity55236 + precursors that acquired a neuronal DA phenotype and up-regulated the expression of @entity66464 and c-ret mRNA. Moreover, the soluble @entity462 -rich domain of Frizzled-8 (a Wnt inhibitor) blocked endogenous Wnts and the effects of @entity6034 a on proliferation and the acquisition of a DA phenotype in precursor cultures. These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles.

Differential regulation of midbrain dopaminergic neuron development by @entity6034 , @entity6035 , and XXXX .

@entity5447 :: ('83571(Tax:10116)', 'Gene') :: ['p27'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity28407 :: ('64566(Tax:10116)', 'Gene') :: ['Wnt-5a'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity6035 :: ('303181(Tax:10116)', 'Gene') :: ['Wnt-3a'] @entity66464 :: ('689388(Tax:10116)', 'Gene') :: ['Ptx3'] @entity6034 :: ('24881(Tax:10116)', 'Gene') :: ['Wnt-1', 'Wnt-1 and -5'] @entity25033 :: ('246060(Tax:10116)', 'Gene') :: ['p57'] @entity12401 :: ('12387(Tax:10090)', 'Gene') :: ['beta-catenin'] @entity68934 :: ('24881;64566', 'Gene') :: ['Wnt-1 and -5a'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity55236 :: ('54278(Tax:10116)', 'Gene') :: ['Nurr1']
@entity28407 :: (64566(Tax:10116),Gene) :: ['Wnt-5a']
