Hedgehog signaling in animal development: paradigms and principles

Ingham, Philip W.; McMahon, Andrew P.

doi:10.1101/gad.938601

Cited by 2,727 publications

(2,545 citation statements)

References 323 publications

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“…To separately investigate the effect of a postnatal reduction in the Shh signaling on ACh or FS, we independently decreased Smo expression in each cell type. Shh binds to Patched homolog 1 or 2, which in turn relieves the repression of the serpentine transmembrane protein Smo, the obligatory Shh transducer (Ingham & McMahon, 2001). Striatal ACh and FS acquire their phenotype during the first 2–3 postnatal weeks in rodents along with the expression of specific markers such as choline acetyltransferase (ChAT, Ach; Phelps, Brady, & Vaughn, 1989) and parvalbumin (PV, FS; Schlösser, Klausa, Prime, & Bruggencate, 1999).…”

Section: Resultsmentioning

confidence: 99%

“…However, the role of GDNF in adult SNpc survival is still controversial (Kopra et al, 2015; Pascual & López‐Barneo, 2015) and needs further clarification. Concomitantly, Sonic hedgehog (Shh), an extracellular ligand involved in cellular specification during development (Ingham & McMahon, 2001), is produced by DA SNpc and is required during late embryogenesis and early postnatal life for the survival and phenotypic maintenance of FS and ACh as well as DA SNpc itself in a non‐cell‐autonomous manner (Gonzalez‐Reyes et al, 2012). However, no defect on striatal interneurons has been associated with the strong DA SNpc degeneration observed in Parkinson's disease, suggesting that further complexity is involved in postnatal neurotrophic maintenance of the striatal modulatory circuit.…”

Section: Introductionmentioning

confidence: 99%

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Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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“…Our double-staining experiments for BMP4-ß-gal and proliferation markers revealed that the BMP4-expressing cells in the subepithelial lamina propria are also mitotically inactive, suggesting that in concert, these epithelial and mesenchymal BMP4 cells adjacent to taste buds may maintain the niche, or signaling center for taste bud stem cells. Interestingly, Miura [32] report that Shh is expressed exclusively in basal cells within taste buds, whereas Ptch1 , a Shh receptor (reviewed by Ingham and McMahon, 2001) [75], is expressed in the epithelial cells outside of taste buds, but adjacent to intragemmal Shh expressing cells. Moreover, mitotic cells, as detected via short term BrdU incorporation are mainly in the Ptch1 expressing region, raising the likelihood that Ptch1 expressing cells comprise the transit amplifying population, and possibly the taste bud stem cells [33].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

Nguyen

Barlow

2010

BMC Neurosci

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BackgroundBone Morphogenetic Protein 4 (BMP4) is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae) and posterior (circumvallate papilla) tongue.ResultsBMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III). BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers and BrdU birthdating.ConclusionOur data suggest that intragemmal BMP4-ß-gal cells in circumvallate papillae are immature taste cells which eventually differentiate into each of the 3 taste cell types, whereas perigemmal BMP4-ß-gal cells in both circumvallate and fungiform papillae may be slow cycling stem cells, or belong to the stem cell niche to regulate taste cell renewal from the proliferative cell population.

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“…However, removing multiple hedgehog activities leads to near absence of all motor neurons (Beattie et al, 1997;Bingham et al, 2001). The roles of other components of the Hh signaling pathway, such as the Patched (Ptc) and Smoothened (Smo) transmembrane proteins, and the Gli transcription factors (Ingham, 1998;Litingtung and Chiang, 2000a;Ingham and McMahon, 2001) in motor neuron induction have also been investigated. In the absence of Hh ligand, Ptc inhibits Smo function, leading to repression of Hh-responsive genes.…”

Section: Induction Of Branchiomotor Neuronsmentioning

confidence: 99%

Turning heads: Development of vertebrate branchiomotor neurons

Chandrasekhar

2003

Developmental Dynamics

164

204

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The cranial motor neurons innervate muscles that control eye, jaw, and facial movements of the vertebrate head and parasympathetic neurons that innervate certain glands and organs. These efferent neurons develop at characteristic locations in the brainstem, and their axons exit the neural tube in well-defined trajectories to innervate target tissues. This review is focused on a subset of cranial motor neurons called the branchiomotor neurons, which innervate muscles derived from the branchial (pharyngeal) arches. First, the organization of the branchiomotor pathways in zebrafish, chick, and mouse embryos will be compared, and the underlying axon guidance mechanisms will be addressed. Next, the molecular mechanisms that generate branchiomotor neurons and specify their identities will be discussed. Finally, the caudally directed or tangential migration of facial branchiomotor neurons will be examined. Given the advances in the characterization and analysis of vertebrate genomes, we can expect rapid progress in elucidating the cellular and molecular mechanisms underlying the development of these vital neuronal networks.

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Hedgehog signaling in animal development: paradigms and principles

Cited by 2,727 publications

References 323 publications

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

Turning heads: Development of vertebrate branchiomotor neurons

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