転写因子Pitx2は,左-右非対称信号への反応として,サイト特有の形態変異を媒介する

M Logan¹, S M Pagán-Westphal, D M Smith

¹Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Cell

|August 26, 1998

まとめ

転写因子Pitx2は,子鳥の胚の左-右非対称性を誘導し,臓器の発達に極めて重要です. その発現は,ノダルとソニック・ヘッジホッグによって制御され,心臓や腸などの臓器の左側発達を左右する.

科学分野:

発達生物学発達生物学について
分子生物学は分子生物学である.
遺伝学遺伝学とは

背景:

左-右非対称性は,オルガノゲネシスにとって根本的であるが,その基礎となるメカニズムは不明である.
転写因子Pitx2は,発達中の臓器の左側に発現することが知られている.

研究の目的:

左から右の特定の臓器の発達を確立するPitx2の役割を調査する.
非対称な信号がPitx2発現とそれに続く形態変異をどのように調節するかを理解する.

主な方法:

オーガノゲネシス中のチキの胚におけるPitx2発現パターンを研究した.
ノダルとソニック・ヘッジホッグのシグナル伝達経路によるPitx2の誘導を調査した.
胚の右側でPitx2を誤って発現させる効果を調べました.

主要な成果:

Pitx2の発現は,左側プレートメソドームと非対称な臓器の左側に局限しています.
ノダルとソニック・ヘッジホッグのシグナル伝達経路はPitx2発現を誘導する.
右側にあるPitx2の誤発現は,心臓のループの逆転,イソメリズム,身体の回転,および腸内サイトを引き起こした.

結論:

Pitx2は,鶏の胚における左-右非対称な臓器発達の重要な媒介である.
NodalやSonic hedgehogのような非対称な信号は,Pitx2の発現を制御し,適切な臓器位置を確保する.

さらに関連する動画

06:21

In Vitro Generation of Somite Derivatives from Human Induced Pluripotent Stem Cells

Published on: April 25, 2019

12:59

Three and Four-Dimensional Visualization and Analysis Approaches to Study Vertebrate Axial Elongation and Segmentation

Published on: February 28, 2021

関連する概念動画

01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...

01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...

02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

02:45

The Ratio of X Chromosome to Autosomes

In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...

02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

関連する実験動画