Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

Joksimovic, Milan; Yun, Beth; Raja, Kavitha; Angela, Anderegg M.; Wendy, Chang W.; Makoto, Taketo M.; McKay, Ronald D.G.; Rajeshwar, Awatramani B.

doi:10.1016/j.ydbio.2009.05.449

Cited by 67 publications

(133 citation statements)

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“…By 9.5 dpc, and through 10.5 dpc, Shh expression and consequent Xgal labeling expands laterally; this lateral expansion is first observed in rostral midbrain sections. Between 10.5 and 11.5 dpc, Shh continues expanding laterally but is downregulated at the midline in the Lmx1aϩ progenitors (15,17,18). Other FP markers, such as Netrin-1, F-spondin, and Foxa2, are also expressed in a similarly broad domain (Fig.…”

Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 84%

“…In coronal sections of Shh::Cre,R26R 9.5-dpc embryos, ␤-galϩ cells are colocalized with Lmx1a and Lmx1b (Fig. 1 D-F) (15). As the Shh domain expands laterally, ␤-gal immunoreactivity is observed in more lateral domains.…”

Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 89%

“…Our initial fate-mapping experiments using a Shh::Cre driver revealed that, in addition to mDA, other neuron types also originated from Shhϩ progenitors (15). To define the repertoire of neurons derived from the Shh domain, we examined postnatal Shh::Cre,R26R midbrain sections (Fig.…”

Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 99%

“…Recent lineage studies have revealed a surprising embryonic origin of mDA at the ventral midline of the midbrain (10,(12)(13)(14)(15). Using a Shh::Cre driver, we have definitively shown that most mDA are derived from the floor plate (FP), operationally defined by the expression of Shh (10,15).…”

mentioning

confidence: 94%

“…Using a Shh::Cre driver, we have definitively shown that most mDA are derived from the floor plate (FP), operationally defined by the expression of Shh (10,15). However, dynamic Shh expression spans a broad domain, and thus it remains to be determined whether this domain is parceled into microdomains, each giving rise to unique cell types.…”

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confidence: 99%

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Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools

Joksimovic

Anderegg

Roy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Midbrain dopamine neurons (mDA) are important regulators of diverse physiological functions, including movement, attention, and reward behaviors. Accordingly, aberrant function of dopamine neurons underlies a wide spectrum of disorders, such as Parkinson's disease (PD), dystonia, and schizophrenia. The distinct functions of the dopamine system are carried out by neuroanatomically discrete subgroups of dopamine neurons, which differ in gene expression, axonal projections, and susceptibility in PD. The developmental underpinnings of this heterogeneity are undefined. We have recently shown that in the embryonic CNS, mDA originate from the midbrain floor plate, a ventral midline structure that is operationally defined by the expression of the molecule Shh. Here, we develop these findings to reveal that in the embryonic midbrain, the spatiotemporally dynamic Shh domain defines multiple progenitor pools. We deduce 3 distinct progenitor pools, medial, intermediate, and lateral, which contribute to different mDA clusters. The earliest progenitors to express Shh, here referred to as the medial pool, contributes neurons to the rostral linear nucleus and mDA of the ventral tegmental area/interfascicular regions, but remarkably, little to the substantia nigra pars compacta. The intermediate Shh؉ progenitors give rise to neurons of all dopaminergic nuclei, including the SNpc. The last and lateral pool of Shh؉ progenitors generates a cohort that populates the red nucleus, Edinger Westphal nucleus, and supraoculomotor nucleus and cap. Subsequently, these lateral Shh؉ progenitors produce mDA. This refined ontogenetic definition will expand understanding of dopamine neuron biology and selective susceptibility, and will impact stem cell-derived therapies and models for PD.dopamine ͉ Sonic hedgehog ͉ lineage ͉ substantia nigra

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Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 84%

Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 89%

Section: Shh Expressing Progenitors Give Rise To Multiple Neuron Typementioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 99%

See 3 more Smart Citations

Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools

Joksimovic

Anderegg

Roy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

121

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Transcatheter aortic valve closure to treat severe aortic regurgitation in a patient failing stage I palliation for hypoplastic left heart syndrome

Riede

Kostelka

Dähnert

2009

Cathet Cardio Intervent

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We present a patient with borderline left ventricle, in whom significant aortic regurgitation after failed attempt of biventricular repair with balloon valvuloplasty and consecutive Norwood stage 1 procedure substantially contributed to persisting hemodynamic instability. Transcatheter closure of the aortic valve using an Amplatzer(R) septal occluder was performed and led to clinical stabilization. At medium-term follow-up, there was neither residual aortic regurgitation nor obstruction of the coronary artery origins.

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Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells

Wullimann

Umeasalugo

2019

J of Comparative Neurology

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Ventralization, a major patterning process in the developing vertebrate neural tube (central nervous system, CNS), depends on Sonic hedgehog (SHH) as a main signaling morphogen. We studied the CNS of late larval and young adult zebrafish in a transgenic shh‐GFP line revealing increased neuroanatomical detail due to the progressed differentiation state compared to earlier stages. Some major findings emerge from the present study. (a) shh –GFP is still expressed along the adult zebrafish CNS neuraxis in most locations seen in larvae. (b) We newly identify a ventroposterior shh pallidal domain representing the basal telencephalic signaling center important for basal ganglia development known in other vertebrates (i.e., the anterior entopeduncular area—basal medial ganglionic eminence of mammals). (c) We further show late‐emerging shh‐GFP positive radial glia cells in the medial zone of the dorsal telencephalon (i.e., the teleostan pallial amygdala). (d) Immunostains for tyrosine hydroxylase demonstrate that there is selective colocalization in adult dopamine cells with shh‐GFP in the posterior tuberculum, including in projection cells to striatum, which represents a striking parallel to amniote mesodiencephalic dopamine cell origin from shh expressing floor plate cells. (e) There is no colocalization of shh and islet1 as shown by respective shh‐GFP and islet1‐GFP lines. (f) The only radially far migrated shh‐GFP cells are located in the preglomerular area. (g) There are no adult cerebellar and tectal shh‐GFP cells confirming their exclusive role during early development as previously reported by our laboratory.

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Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

Cited by 67 publications

References 0 publications

Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools

Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools

Transcatheter aortic valve closure to treat severe aortic regurgitation in a patient failing stage I palliation for hypoplastic left heart syndrome

Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells

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