XB-ART-55911Genesis April 25, 2019; e23296.
What are the roles of retinoids, other morphogens, and Hox genes in setting up the vertebrate body axis?
This article is concerned with the roles of retinoids and other known anterior-posterior morphogens in setting up the embryonic vertebrate anterior-posterior axis. The discussion is restricted to the very earliest events in setting up the anterior-posterior axis (from blastula to tailbud stages in Xenopus embryos). In these earliest developmental stages, morphogen concentration gradients are not relevant for setting up this axis. It emerges that at these stages, the core patterning mechanism is timing: BMP-anti BMP mediated time space translation that regulates Hox temporal and spatial collinearities and Hox-Hox auto- and cross- regulation. The known anterior-posterior morphogens and signaling pathways--retinoids, FGF''s, Cdx, Wnts, Gdf11 and others--interact with this core mechanism at and after space-time defined "decision points," leading to the separation of distinct axial domains. There are also other roles for signaling pathways. Besides the Hox regulated hindbrain/trunk part of the axis, there is a rostral part (including the anterior part of the head and the extreme anterior domain [EAD]) that appears to be regulated by additional mechanisms. Key aspects of anterior-posterior axial patterning, including: the nature of different phases in early patterning and in the whole process; the specificities of Hox action and of intercellular signaling; and the mechanisms of Hox temporal and spatial collinearities, are discussed in relation to the facts and hypotheses proposed above.
PubMed ID: 31021058
Article link: Genesis
Genes referenced: birc6 clock gbx2.1 gbx2.2 gdf11.2 hoxa11 hoxa7 hoxb4 hoxb5 hoxb7 hoxb8 hoxb9 hoxc10 hoxc12 hoxc6 hoxd1 hoxd10 hoxd13 hoxd4 muc2 nog otx2 six3 tst
GO keywords: axis specification
Article Images: [+] show captions
|Figure 1. Timing, axial patterning, and time-space translation. Above: The structure of the vertebrate A–P axis: domains with significant Hox genes and other markers. An unexpected element is introduced by the newly characterized extreme anterior domain (EAD), which makes the face. This is shown as the most anterior part of the straight axis. Actually, the anterior end of the dorsal A–P axis bends backward around to the ventral side of the embryo to face posteriorly like the handle of a walking stick (not shown). A. Head: anterior head (corresponding to telencephalon, diencephalon, mesencephalon). P. Head: posterior head (corresponding to anterior rhombencephalon, occipital somites). Neck: cervical somites, posterior rhombencephalon, Thorax: thoracic vertebrae, anterior spinal cord. Abdomen: Lumbar and sacral regions, spinal cord. Tail: coccygeal vertebrae, spinal cord. Above and below: Time space translation. A biological timer, represented by the clock face below, proceeds from 1 to 12 (red numbers). The timer starts with information needed for making the EAD, proceeds to the anterior head, then to posterior head, then to neck, then to thorax, then abdomen, then tail. The timer needs BMP to function, so occurs in tissues with high BMP (yellow/orange). Anti–BMP factors (blue) interact with the timer sequentially to freeze the identities of an A–P sequence of axial zones. In the axial sequence, the Hox genes are each both a component of the timer at their appropriate times and are sequentially involved in setting up the A–P sequence of axial zones. The genes involved in time space translation in the EAD‐head zones are unknown. The head and tail of the A–P timer are close together because of their representation on a clock face. No statement about molecular identities is intended.|
|Figure 2. Xenopus Hox sequences for axial cascade phenotypes relating to domain boundaries. Above: Wild type Hox sequence. Next down: Hox1 loss of function (LOF; all 3 Hox1 genes knocked down by morpholinos (MOs). The axis from Hox1 backward is compromised. The dotted line indicates there is still reduced residual expression for some posterior Hox genes. Next down: Hoxc6 LOF (MO). The axis from Hoxc6 backward is compromised/deleted. Next down: Hoxb9 gain of function (GOF) by ectopic expression of Hoxb9 in Hox‐free dorsalised embryos. A partial posterior axis is generated, starting with Hoxb9.|
|Figure 4. Growth factors and the axial domains. The anterior head (A. Head)/posterior head (P. Head) boundary is influenced by active retinoids/retinoic acid (RA) and Wnt (8 or 3A). Both turn posterior head on. The neck/thorax boundary is influenced by RA (thorax off) and FGF/Cdx (thorax on). The thorax/abdomen boundary is influenced by Wnt. The abdomen/tail boundary is influenced by GDF11 (tail on) and RA, which blocks the transition of abdomen to tail, that is, it changes tail to limbs or truncates the axis.|