Once and again: Retinoic acid signaling in the developing and regenerating olfactory pathway

Rawson, Nancy E.; LaMantia, Anthony S.

doi:10.1002/neu.20236

Cited by 42 publications

(35 citation statements)

References 165 publications

(188 reference statements)

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“…This is highly similar to the situation observed in the hindbrain, and further supports the idea of a RA gradient leading to progressively weaker activation of the RARE-Cre transgene toward more anterior regions of the otocyst. Retinoid signaling has also been implicated in regulating the differentiation, stability, or regeneration in the olfactory pathway from embryogenesis through adulthood development, possibly by acting on olfactory neural stem cells (Rawson and LaMantia, 2006, and references therein). Our data using the RARECre;R26R system revealing ubiquitous labeling through the developing olfactory epithelium, support the theory that retinoid signaling has taken place early in stem/progenitor populations for olfactory neurons and sustentacular cells.…”

Section: Discussionmentioning

confidence: 99%

“…Our data using the RARECre;R26R system revealing ubiquitous labeling through the developing olfactory epithelium, support the theory that retinoid signaling has taken place early in stem/progenitor populations for olfactory neurons and sustentacular cells. As vitamin A therapy accelerates functional recovery in animals with olfactory system damage (Rawson and LaMantia, 2006), ubiquitous labeling might indicate that this region could be responsive to a therapeutic activity of RA. A more unexpected observation was made by examining the developing vibrissae (specialized hair follicles with mechanosensory properties).…”

Section: Discussionmentioning

confidence: 99%

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Fate of retinoic acid–activated embryonic cell lineages

Dollé

Fraulob

Gallego-Llamas

et al. 2010

Developmental Dynamics

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Retinoic acid (RA), a vitamin A derivative, is synthesized by specific cell populations and acts as a diffusible embryonic signal activating ligand‐inducible transcription factors, the RA receptors (RARs). RA‐activatable transgenic systems have revealed many discrete, transient sites of RA action during development. However, there has been no attempt to permanently label the RA‐activated cell lineages during mouse ontogenesis. We describe the characterization of a RA‐activatable Cre transgene, which through crosses with a conditional reporter strain (the ROSA26R lacZ reporter), leads to a stable labeling of the cell populations experiencing RA signaling during embryogenesis. RA response‐element (RARE) ‐driven Cre activity mimics at early stages the known activity of the corresponding RARE‐lacZ transgene (Rossant et al.,1991). Stable labeling of the Cre‐excised cell populations allows to trace the distribution of the RA‐activated cell lineages at later stages. These are described in relationship with current models of RA activity in various developmental systems, including the embryonic caudal region, limb buds, hindbrain, sensory organs, and heart. Developmental Dynamics 239:3260–3274, 2010. © 2010 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fate of retinoic acid–activated embryonic cell lineages

Dollé

Fraulob

Gallego-Llamas

et al. 2010

Developmental Dynamics

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“…These collective results support the possibility that ATF5 directs transcription of some OSN-specific genes by direct binding to the target gene promoter. Retinoic acid promotes olfactory identity and is required for olfactory function (18). Fig.…”

Section: Atf5mentioning

confidence: 99%

Transcription factor ATF5 is required for terminal differentiation and survival of olfactory sensory neurons

Wang

Ou²,

Zhu

et al. 2012

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

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Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding family of transcription factors, which compose a large group of basic region leucine zipper proteins whose members mediate diverse transcriptional regulatory functions. ATF5 has a well-established prosurvival activity and has been found to be overexpressed in several human cancers, in particular glioblastoma. However, the role(s) of ATF5 in development and normal physiology are unknown. Here we address this issue by deriving and characterizing homozygous Atf5 knockout mice. We find that Atf5 −/− pups die neonatally, which, as explained below, is consistent with an olfactory defect resulting in a competitive suckling deficit. We show that Atf5 is highly expressed in olfactory sensory neurons (OSNs) in the main olfactory epithelium starting from embryonic stage 11.5 through adulthood. Immunostaining experiments with OSN-specific markers reveal that ATF5 is expressed in some immature OSNs and in all mature OSNs. Expression profiling and immunostaining experiments indicate that loss of Atf5 leads to a massive reduction in mature OSNs resulting from a differentiation defect and the induction of apoptosis. Ectopic expression of Atf5 in neural progenitor cells induces expression of multiple OSN-specific genes. Collectively, our results suggest a model in which Atf5 is first expressed in immature OSNs and the resultant ATF5 functions to promote differentiation into mature OSNs. Thus, ATF5 is required for terminal differentiation and survival of OSNs.hyposmia | olfaction | neonatal death | olfactory marker protein | TUJ1 A ctivating transcription factor 5 (ATF5; also known as ATFx) is a member of the ATF/cAMP response element-binding (CREB) family of transcription factors, which compose a large group of basic region leucine zipper (bZIP) proteins whose members mediate diverse transcriptional regulatory functions (reviewed in ref. 1). A role for ATF5 in promoting cell survival was first suggested from expression profiling experiments, which revealed that Atf5 was the gene most down-regulated in interleukin-3-dependent murine hematopoietic cells following apoptosis induction elicited by cytokine deprivation (2). Functional experiments demonstrated that the prosurvival function of ATF5 results from its ability to inhibit apoptosis (3).A variety of subsequent studies have shown that ATF5 is overexpressed in, and contributes to the survival of, several human cancer cell lines and solid tumors, in particular glioblastoma (4, 5). The high level of ATF5 in brain tumors, coupled with the absence of ATF5 expression in mature neurons, has raised the possibility that ATF5 may be a therapeutic target for treatment of glioblastoma. Consistent with this idea, inhibiting ATF5 function, using either a dominant-negative mutant or a small interfering RNA, causes massive apoptotic death of rodent and human glioblastoma cell lines. By contrast, comparable loss of ATF5 function does not affect survival of cultured neurons or glial cells (6, 7).A rigo...

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“…Retinoic acid (RA), a derivative of vitamin A, is produced by the front-nasal region and considered to be a key molecule to trigger the retinoid-dependent signaling (reviewed in Rawson & LaMantia 2006). Importantly, reporter gene expression responding to the RA-signaling is not detected in the front-nasal region of the Sey/Sey mutant (Anchan et al 1997).…”

Section: Role Of Pax6 In the Developing Olfactory Placode And Epitheliummentioning

confidence: 99%

Role of a transcription factor Pax6 in the developing vertebrate olfactory system

2007

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The olfactory system is responsible for capturing and processing odorant information, which significantly influences a variety of behaviors in animals. The vertebrate olfactory system consists of several neuronal components including the olfactory epithelium, olfactory bulb and olfactory cortex, which originate from distinct embryonic tissues. The transcription factor Pax6 is strongly expressed in the embryonic and postnatal olfactory systems, and regulates neuronal specification, migration and differentiation. Here we review classical and recent studies focusing on the role of Pax6 in the developing olfactory system, and highlight the cellular and molecular mechanisms underlying the highly coordinated developmental processes of the vertebrate olfactory system.

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Once and again: Retinoic acid signaling in the developing and regenerating olfactory pathway

Cited by 42 publications

References 165 publications

Fate of retinoic acid–activated embryonic cell lineages

Fate of retinoic acid–activated embryonic cell lineages

Transcription factor ATF5 is required for terminal differentiation and survival of olfactory sensory neurons

Role of a transcription factor Pax6 in the developing vertebrate olfactory system

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