Tulp3 is a critical repressor of mouse hedgehog signaling

Cameron, Don; Pennimpede, Tracie; Petkovich, Martin

doi:10.1002/dvdy.21926

Cited by 45 publications

(42 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The staining pattern obtained with this antibody in the developing mouse neural tube (Cameron et al, 2009), including the forebrain (present results), is identical to that obtained with in situ hybridization (Ericson et al, 1997;Stoykova et al, 2000;Puelles et al, 2000;present results: compare Fig. 1 and Fig.…”

Section: Antibody Characterizationsupporting

confidence: 88%

Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons

Bupesh

Abellán

Medina

2011

J of Comparative Neurology

182

View full text Add to dashboard Cite

The central extended amygdala is the major output center for telencephalic control of ingestion, fear responses, stress, and anxiety. In spite of the abundant data supporting the similarity in neurochemistry, connections, and function along the extended amygdala, embryological support for this continuum is lacking. By using a combination of in vitro migration assays, in situ hybridization, and immunostaining, here we show that its major components, including central amygdala and lateral bed nucleus of the stria terminalis (BST), are mosaics formed by different proportions of dorsal lateral ganglionic eminence (LGE)-, ventral LGE-, and medial ganglionic eminence (MGE)-derived principal neurons. The dorsal LGE produces Pax6-expressing neurons that primarily populate lateral parts of the central extended amygdala, including the capsular and part of lateral central amygdala, but also produces a few cells for the lateral BST. Based on correlation with preproenkephalin, many of these cells are likely enkephalinergic. The ventral LGE produces Islet1-expressing neurons that populate primarily the central and medial parts of the central amygdala but also produces numerous neurons for the lateral BST. Correlation with corticotropin-releasing factor suggests that these neurons express this neuropeptide. The MGE produces the majority of neurons of the lateral BST, but its ventrocaudal subdivision also produces an important subpopulation of projection neurons containing somatostatin for medial aspects of the central amygdala. Thus, distinct principal neurons originate in different embryonic domains, but the same domains contribute neurons to most subdivisions of the central extended amygdala, which may explain the similarity in neurochemistry and connections along the corridor.

show abstract

Section: Antibody Characterizationsupporting

confidence: 88%

Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons

Bupesh

Abellán

Medina

2011

J of Comparative Neurology

182

View full text Add to dashboard Cite

show abstract

“…Tulp3, IFT-A components such as Ift139, and Gpr161 are all negative regulators of ciliary Hh signaling (Mukhopadhyay et al 2013; Norman et al 2009; Patterson et al 2009; Cameron et al 2009; Qin et al 2011; Tran et al 2008; Liem Jr. et al 2012). In addition to limiting ciliary PI(4,5)P 2 levels, Inpp5e limits the ciliary localization of these negative regulators and is required for normal Hh signal transduction.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of Shh to its receptor Patched1 (Ptch1) causes the ciliary accumulation of Smoothened (Smo) and the ciliary exit of Gpr161, thereby inducing the activation of Gli transcription factors, which move from the cilium to the nucleus and induce the Hh transcriptional program. Ciliary localization of Gpr161 requires a ciliary trafficking complex that includes Tulp3 and the intraflagellar transport complex A (IFT-A) (Mukhopadhyay et al 2010 and 2013; Norman et al 2009; Patterson et al 2009; Cameron et al 2009; Qin et al 2011; Tran et al 2008; Liem Jr. et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog Signaling

et al. 2015

View full text Add to dashboard Cite

SUMMARY Primary cilia interpret vertebrate Hedgehog (Hh) signals. Why cilia are essential for signaling is unclear. One possibility is that some forms of signaling require a distinct membrane lipid composition, found at cilia. We found that the ciliary membrane contains a particular phosphoinositide, PI(4)P, whereas a different phosphoinositide, PI(4,5)P2, is restricted to the membrane of the ciliary base. This distribution is created by Inpp5e, a ciliary phosphoinositide 5-phosphatase. Without Inpp5e, ciliary PI(4,5)P2 levels are elevated and Hh signaling is disrupted. Inpp5e limits the ciliary levels of inhibitors of Hh signaling, including Gpr161 and the PI(4,5)P2-binding protein Tulp3. Increasing ciliary PI(4,5)P2 levels or conferring the ability to bind PI(4)P on Tulp3 increases the ciliary localization of Tulp3. Lowering Tulp3 in cells lacking Inpp5e reduces ciliary Gpr161 levels and restores Hh signaling. Therefore, Inpp5e regulates ciliary membrane phosphoinositide composition, and Tulp3 reads out ciliary phosphoinositides to control ciliary protein localization, enabling Hh signaling.

show abstract

“…However, the molecular function of these genes is poorly understood. Tulp3 has been described recently as a negative regulator of Hh signaling in the mouse embryo (Cameron et al 2009;Norman et al 2009;Patterson et al 2009). Genetic epistasis experiments suggest that, similar to the IFT-A subunit Thm1, Tulp3 restricts Gli2 activity in an IFT-dependent manner downstream from Sonic hedgehog (Norman et al 2009;Patterson et al 2009).…”

mentioning

confidence: 99%

TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia

Mukhopadhyay¹,

Wen²,

Chih³

et al. 2010

Genes Dev.

362

547

View full text Add to dashboard Cite

Primary cilia function as a sensory signaling compartment in processes ranging from mammalian Hedgehog signaling to neuronal control of obesity. Intraflagellar transport (IFT) is an ancient, conserved mechanism required to assemble cilia and for trafficking within cilia. The link between IFT, sensory signaling, and obesity is not clearly defined, but some novel monogenic obesity disorders may be linked to ciliary defects. The tubby mouse, which presents with adult-onset obesity, arises from mutation in the Tub gene. The tubby-like proteins comprise a related family of poorly understood proteins with roles in neural development and function. We find that specific Tubby family proteins, notably Tubby-like protein 3 (TULP3), bind to the IFT-A complex. IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. Both IFT-A and membrane phosphoinositide-binding properties of TULP3 are required for ciliary GPCR localization. TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo, and the TULP3–IFT-A interaction suggests how these proteins cooperate during neural tube patterning.

show abstract

Tulp3 is a critical repressor of mouse hedgehog signaling

Cited by 45 publications

References 58 publications

Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons

Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons

Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog Signaling

TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia

Contact Info

Product

Resources

About