Hindbrain patterning involves graded responses to retinoic acid signalling

Several recent studies have shown that retinoic acid signalling is required for correct patterning of the hindbrain. However, the data from these studies are disparate and the precise role of retinoic acid signalling in patterning the anteroposterior axis of the neural tube remains uncertain. To help clarify this issue, we have cultured a staged series of chick embryos in the presence of an antagonist to the all three retinoic acid receptors. Our data indicate that retinoic acid is the transforming signal involved in the expansion of posterior hindbrain structures. We find that the hindbrain region of the neural tube down to the level of the sixth somite acquires the identity of rhombomere 4 when retinoic acid signalling is blocked. Specification of future rhombomere boundaries has a retinoic acid dependency between stage 5 and stage 10+ that is lost progressively in an anterior-to-posterior sequence. Furthermore, the application of various concentrations of antagonist shows that successively more posterior rhombomere boundaries require progressively higher concentration of endogenous retinoic acid for their correct positioning, a result that strengthens the hypothesis that a complex retinoid gradient acts to pattern the posterior hindbrain. Our dissection of early retinoic acid functions allows us to re-interpret the wide disparity of hindbrain phenotypes previously observed in various models of retinoic acid deficiency.

Download Full-text

Genesis and prevention of spinal neural tube defects in the curly tail mutant mouse: involvement of retinoic acid and its nuclear receptors RAR-beta and RAR-gamma

Development ◽

10.1242/dev.121.3.681 ◽

1995 ◽

Vol 121 (3) ◽

pp. 681-691

Author(s):

W.H. Chen ◽

G.M. Morriss-Kay ◽

A.J. Copp

Keyword(s):

Retinoic Acid ◽

Neural Tube ◽

Neural Tube Defects ◽

In Situ Hybridisation ◽

Tail Bud ◽

Retinoic Acid Signalling ◽

All Trans Retinoic Acid ◽

Posterior Neuropore ◽

Computerised Image Analysis ◽

Curly Tail

A role for all-trans-retinoic acid in spinal neurulation is suggested by: (1) the reciprocal domains of expression of the retinoic acid receptors RAR-beta and RAR-gamma in the region of the closed neural tube and open posterior neuropore, respectively, and (2) the preventive effect of maternally administered retinoic acid (5 mg/kg) on spinal neural tube defects in curly tail (ct/ct) mice. Using in situ hybridisation and computerised image analysis we show here that in ct/ct embryos, RAR-beta transcripts are deficient in the hindgut endoderm, a tissue whose proliferation rate is abnormal in the ct mutant, and RAR-gamma transcripts are deficient in the tail bud and posterior neuropore region. The degree of deficiency of RAR-gamma transcripts is correlated with the severity of delay of posterior neuropore closure. As early as 2 hours following RA treatment at 10 days 8 hours post coitum, i.e. well before any morphogenetic effects are detectable, RAR-beta expression is specifically upregulated in the hindgut endoderm, and the abnormal expression pattern of RAR-gamma is also altered. These results suggest that the spinal neural tube defects which characterise the curly tail phenotype may be due to interaction between the ct gene product and one or more aspects of the retinoic acid signalling pathway.

Download Full-text

LSC - 2021 - Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach

10.1183/13993003.congress-2021.pa3624 ◽

2021 ◽

Author(s):

Mongey Róisín ◽

Sally Yunsun Kim ◽

Diana Van Der Plaat ◽

Cosetta Minelli ◽

Charlotte Dean ◽

...

Keyword(s):

Retinoic Acid ◽

Vitamin A ◽

Multidisciplinary Approach ◽

Retinoic Acid Signalling

Download Full-text

The Role of Retinoic Acid Receptors in Myeloid Differentiation

Transcription Factors ◽

10.1002/0471223883.ch10 ◽

2003 ◽

pp. 149-161

Author(s):

Steven J. Collins ◽

Barton S. Johnson ◽

Louise E. Purton

Keyword(s):

Retinoic Acid ◽

Retinoic Acid Receptors ◽

Myeloid Differentiation

Download Full-text

The role of retinoids and retinoic acid receptors in normal hematopoiesis

Leukemia ◽

10.1038/sj.leu.2402718 ◽

2002 ◽

Vol 16 (10) ◽

pp. 1896-1905 ◽

Cited By ~ 105

Author(s):

SJ Collins

Keyword(s):

Retinoic Acid ◽

Retinoic Acid Receptors

Download Full-text

Relationship between Wnt-1 and En-2 expression domains during early development of normal and ectopic met-mesencephalon

Development ◽

10.1242/dev.115.4.999 ◽

1992 ◽

Vol 115 (4) ◽

pp. 999-1009 ◽

Cited By ~ 23

Author(s):

L. Bally-Cuif ◽

R.M. Alvarado-Mallart ◽

D.K. Darnell ◽

M. Wassef

Keyword(s):

In Situ Hybridization ◽

Neural Tube ◽

Expression Patterns ◽

Mouse Embryos ◽

Chick Embryos ◽

Expression Domain ◽

General Role ◽

Maximal Expression

Grafting a met-mesencephalic portion of neural tube from a 9.5-day mouse embryo into the prosencephalon of a 2-day chick embryo results in the induction of chick En-2 (ChickEn) expression in cells in contact with the graft (Martinez et al., 1991). In this paper we investigate the possibility of Wnt-1 being one of the factors involved in En-2 induction. Since Wnt-1 and En-2 expression patterns have been described as diverging during development of the met-mesencephalic region, we first compared Wnt-1 and En-2 expression in this domain by in situ hybridization in mouse embryos after embryonic day 8.5. A ring of Wnt-1-expressing cells is detected encircling the neural tube in the met-mesencephalic region at least until day 12.5. This ring consistently overlapped with the En-2 expression domain, and corresponds to the position of this latter gene's maximal expression. We subsequently studied ChickEn ectopic induction in chick embryos grafted with various portions of met-mesencephalon. When the graft originated from the level of the Wnt-1-positive ring, ChickEn induction was observed in 71% of embryos, and in these cases correlated with Wnt-1 expression in the grafted tissue. In contrast, this percentage dropped significantly when the graft was taken from more rostral or caudal parts of the mesencephalic vesicle. Taken together, these results are compatible with a prolonged role of Wnt-1 in the specification and/or development of the met-mesencephalic region, and show that Wnt-1 could be directly or indirectly involved in the regulation of En-2 expression around the Wnt-1-positive ring during this time. We also provide data on the position of the Wnt-1-positive ring relative to anatomical boundaries in the neural tube, which suggest a more general role for the Wnt-1 protein as a positional signal involved in organizing the met-mesencephalic domain.

Download Full-text

Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis

Molecular Biology of the Cell ◽

10.1091/mbc.e14-06-1144 ◽

2015 ◽

Vol 26 (5) ◽

pp. 978-992 ◽

Cited By ~ 7

Author(s):

Guang Wang ◽

Yan Li ◽

Xiao-Yu Wang ◽

Manli Chuai ◽

John Yeuk-Hon Chan ◽

...

Keyword(s):

Chick Embryo ◽

Embryonic Development ◽

Neural Crest ◽

Embryo Development ◽

Neural Tube ◽

Neural Crest Cells ◽

Chick Embryos ◽

Early Chick Embryo

This is the first study of the role of BRE in embryonic development using early chick embryos. BRE is expressed in the developing neural tube, neural crest cells, and somites. BRE thus plays an important role in regulating neurogenesis and indirectly somitogenesis during early chick embryo development.

Download Full-text

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms20122921 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2921 ◽

Cited By ~ 7

Author(s):

Conserva ◽

Anelli ◽

Zagaria ◽

Specchia ◽

Albano

Keyword(s):

Retinoic Acid ◽

Acute Promyelocytic Leukemia ◽

Chromosomal Rearrangements ◽

Therapy Response ◽

Promyelocytic Leukemia ◽

Retinoic Acid Receptors ◽

Hematopoietic Stem ◽

Vitamin A Metabolism ◽

Hematological Neoplasms

The family of retinoic acid receptors (RARs: RARα, -β, and -γ) has remarkable pleiotropy characteristics, since the retinoic acid/RARs pathway is involved in numerous biological processes not only during embryonic development, but also in the postnatal phase and during adulthood. In this review, we trace the roles of RA/RARs signaling in the immune system (where this pathway has both an immunosuppressive role or is involved in the inflammatory response), in hematopoiesis (enhancing hematopoietic stem cell self-renewal, progenitor cells differentiation or maintaining the bone marrow microenvironment homeostasis), and in bone remodeling (where this pathway seems to have controversial effects on bone formation or osteoclast activation). Moreover, in this review is shown the involvement of RAR genes in multiple chromosomal rearrangements generating different fusion genes in hematological neoplasms, with a particular focus on acute promyelocytic leukemia and its variant subtypes. The effect of different RARs fusion proteins on leukemic transformation, on patients’ outcome, and on therapy response is also discussed.

Download Full-text