Developmental Biology 第四章果蝇胚胎早期 发育的分子基础
Developmental Biology 第四章 果蝇胚胎早期 发育的分子基础
Developmental Biology 、果蝇胚胎发育概况 Fig 5.1 Patterning of the Drosophila Dorsal embryo. The body plan is patterned along two distinct axes. The antero- posterior and dorso-ventral axes are at right angles to each other and are laid down in the egg. In the early embryo. the dorso-ventral axis is divided into four regions: mesoderm(red), ventral ectoderm (yellow), dorsal ectoderm (orange), and amnioserosa (an extra mbryo amnioserosa dorsal ectoderm tents embryonic membrane, green).The ventral ectoderm gives rise to both ventral epidermis and neural tissue. the dorsal ectoderm to epidermis, The Head antero-posterior axis becomes divided into different regions that later give rise prospective to the head, thorax, and abdomen. After postenor gut the initial division into broad body regions, tenor gut ventral ectoderm segmentation begins, The future segments endoderm mesoderm can be visualized as transverse stripes by staining for specific gene activity hese strpes demarcate 14 parasegment First instar larva 10 of which are marked. The embryo develops into a segmented larva. By the time the larva hatches, the 14 para. segments have been converted into telson thoracic (T1-T3)and abdominal (A1-A8) segments, which are offset from the T213A1A2A3M45A4)4 parasegments by one half segment. Different segments are distinguished by the patterns of bristles and denticles on the cuticle. Specialized structures, the Thoracic segments acron and telson, develop at the head and tail ends, respectively
Developmental Biology 一、果蝇胚胎发育概况
Developmental Biology 二、胚胎躯体轴线的建立由母体基因决定 Maternal ne Examples of regions of gene activity Fig 5.2 The sequential expression of different sets of genes estab ishes th body plan along the antero-posterio axis. After fertilization bicoid (bcd) g母体基因产物量或 coid mRNA, are translated. They provide positional information whi activates the zygotic gones. The four 活性形成空间分布 bp3上的差异,在A Zygotic genes gap genes, the pair-rule genes, the segment polarity genes, and the selector. or homeotic, genes. The gap P和D-V轴线的不 hunchback ihoj 1同区域激活不同的 genes define regional differences that nd foreshadow 基因,使不同区域 Pair-rule egment polarity genes elaborate the ttern in the segments, and segment 的基因活性谱不同 is determined by the selector maem而出现分化。 Selector abdominal/A (abd-A)
Developmental Biology 二、胚胎躯体轴线的建立由母体基因决定 母体基因产物量或 活性形成空间分布 上的差异，在A－ P和D－V轴线的不 同区域激活不同的 基因，使不同区域 的基因活性谱不同 而出现分化
Developmental Biology 1.A-P轴线由三类母体基因控制:突变鉴定 anterior class, posterior class, terminal class. wild-type egg fate ma wild-type larva Fig 5.3 The effects of mutations in the maternal gene system. Mutations in maternal genes lead to deletions and abnormalities in anterior, posterior, or terminal structures, The wild-type fate give rise to particular regions ang map shows which regions of the lc son head abdomen structures in the larva. Regions that are thorax affected in mutant eggs and which lead to lost or altered structures in the larva Mutant eggs Mutant embryos Regions affected are shaded in red. In bicoid mutants there is a partial loss of antenor structures bicod mutant and the appearance of a postenor structure-the telson-at the anterior end, nanos mutants lack a large part of the posterior region. torso mutants lack both acron and telson nanos mutant
Developmental Biology 1. A－P轴线由三类母体基因控制：突变鉴定 anterior class, posterior class, terminal class
Table 9.1 Maternal effect genes that effect the anterior-posterior polarity of the Drosophila embryo Gene Mutant phenotype Proposed function and structure ANTERIOR GROUP bicoid (bcd) Head and thorax deleted, replaced by Graded anterior morphogen; inverted telson contains homeodomain: represses caudal exuperantia(exu) Anterior head structures deleted Anchors bicoid mRNA swallow(swa) Anterior head structures deleted Anchors bicoid mRNP POSTERIOR GROUP nanos(nos) o abdomen Posterior morphogen represses hunchback tudor(tud) No abdomen, no pole cells Localization of Nanos oskar(osk) No abdomen, no pole cells Localization of Nanos sa(vas) No abdomen, no pole cells; oogenesis defective Localization of Nanos valois(val) No abdomen, no pole cells; cellularization Stabilization of the Nanos localization defective complex pumilio(pum) No abdomen Helps Nanos protein bind hunchback message caudal (cad) No abdomen Activates posterior terminal genes TERMINAL GROUP torso(to No termini Possible morphogen for termini trunk(trk) No termini Transmits Torsolike signal to torso fs(I)NasrarUSs(I)N] No termini: collapsed eggs Transmits Torsolike signal to Torso fs( 1)poleholel s(1)ph) No termini; collapsed eggs Transmits Torsolike signal to torso After Anderson 1989
Developmental Biology
Developmental Biology 2. Bicoid基因提供A一P轴线形态素梯度 Fig. 5. 4 The bicoid gene is necessary for the development of anterior structures. Embryos whose mothers ack the bicoid gene lack anterior regions upper middle panels). Transfer of anterior cytoplasm from wild-typ embryos to bicoid mutant embryo causes some anterior structure to Wild-type egg Wild-type larva develop at the site of injection(lower middle panels). If wild-type anterior cytoplasm is transplanted to the middle of a bicoid mutant egg or early embryo. bicoid编码 head structures develop at the site of injection, flanked on both sides by thoracic-type segments( bottom panels) 种转录因子 These results can be interpreted of the anterior cytoplasm setting gradient of bicoid protein with the point at the site of injection(see graphs. bicoid mutant egg bicoid mutant larva 其突变体缺失 bottom left panel) 头胸结构,原 头区由尾区取 代 Wild-type egg bicoid mutant egg Some anterior structures develop Wild-type egg bicoid mutant egg Thoracic Head Thoracic segments
Developmental Biology 2. Bicoid基因提供A－P轴线形态素梯度 Bicoid编码一 种转录因子。 其突变体缺失 头胸结构，原 头区由尾区取 代
Developmental Biology Bicoid mRNA和蛋白质的分布 Maternal bicoid mRNA Fig 5.5 The distribution of the 在未受精卵中, mat nea miia tof bicoid in the egg bicoid mRNAZE after fertilization. Top panel: the mRNA位在胞质前端; A P is visualized by in situ hybridization Middle panel: the bicoid protein is 其受精后翻译 stained with a labeled antibody Bottom panel: translation of bicoid mRNA and 出的蛋白质沿 diffusion of bicoid protein from its site of AP轴扩散,形 bicoid protein synthesis produces an antero-posterior gradient of bicoid protein in the embryo.成浓度梯度, Scale bars =0.1 mm. Photographs courtesy of R. Lehmann, from 为胚胎的后续 Suzuki, D.T., et al. 1996 分化提供位置 信息。 Bicoid是控制头胸发育的一个关键母体基因,其 maternal bicoid mRNA 不同浓度开启不同合子基因的表达。其它的前 区母体基因主要涉及 bicoid mRNA在未受精卵中 uap的定位及控制其翻译
Developmental Biology Bicoid mRNA和蛋白质的分布 在未受精卵中， bicoid mRNA定 位在胞质前端； 其受精后翻译 出的蛋白质沿 AP轴扩散，形 成浓度梯度， 为胚胎的后续 分化提供位置 信息。 Bicoid是控制头胸发育的一个关键母体基因，其 不同浓度开启不同合子基因的表达。其它的前 区母体基因主要涉及bicoidmRNA在未受精卵中 的定位及控制其翻译
Developmental Biology 3. Nanos和 Cauda蛋白梯度控制后区结构 Fig 5.6 Establishment of a maternal Maternal mRNA expression gradient in hunchback protein nanos Protein expression Left panel: maternal hunchback mRNA (turquoise) is present at a relatively low level throughout the egg, whereas nanos mRNA (yellow) is located posteriorly. The photograph is an in situ hybridization showing nanos mRNA Right panel: after fertilization, nanos mRNA is translated and nanos protein blocks translation of hunchback mRNA in the posterior regions giving rise to a shallow antero-posteror gradient in matemal hunchback protein The photograph shows the distribution of nanos protein detected with a labeled hunchback hunchback nanos antibody Photographs courtesy of R. Lehmann, from Suzuki, D.T. et al: 1996 Nanos决定后部区的发育,它在受精后形成P一A浓度梯度,其作用是与 hunchback mrna结合,阻止后者在后区的翻译,帮助形成 Hunchback蛋白梯度
Developmental Biology 3. Nanos和Caudal蛋白梯度控制后区结构 Nanos决定后部区的发育，它在受精后形成P－A浓度梯度，其作用是与 hunchback mRNA结合，阻止后者在后区的翻译，帮助形成Hunchback蛋白梯度。 nanos
Developmental Bin Nanos控制 hunchback mRNA翻译的机制 Figure 9.16 Control of hunchback mRNA translation by Nanos. In the anterior of the embryo, Pumilio protein binds to the Nanos Response Element(NRE) in the 3 UTR of the hunchback mes- sage, and the message is polyadenylated normally. This polyadenylated message can be trans lated into Hunchback protein In the posterior of the embryo, where Nanos protein is found, Nanos binds to Pumilio to cause the deadenylation of the hunchback message. This prevents the translation of the hunchback message. After Wreden et al. 1997. ANTERIOR POSTERIOR Nanos response element Hunchback Pumilio Nanos mRNA AAAAA Adenylation Deadenylation AAA Translation No translation Hunchback protein o Hunched Promotes anterior Allows abdominal structures formation
Developmental Biology Nanos控制hunchback mRNA翻译的机制
Developmental Biology A→P轴线形成模式 Figure 9.11 (A)Oocyte mRNAS (C) A model of anterior-posterior pattern generation by the Drosophila maternal hunchback mRNA ANTERIOR effect genes. (A)The bicoid, nanos, hunchback, and caudal messenger RNAs s f hicoid mRNA are placed in the oocyte by the ovarian a caudal Cortex nurse cells. The bicoid message is se- mRNA Grauzone questered anteriorly The nanos mes- g bicoid nanos Staufen caudal mRNA sage is sent to the posterior pole. (B) 8 RNA mRNA Upon translation, the Bicoid protein Bicoid prote gradient extends from anterior to pos Anterior Posterior terior,and the Nanos protein gradient Caudal protein Nanos inhibits the translation of the (B)Early cleavage embryo proteins POSTERIOR hunchback message(in the posterior) while Bicoid prevents the translation of t nanos mRNA the caudal message(in the anterior) Hunchback Oskar hunchback This inhibition results in opposing nRNA Caudal and Hunchback gradients. The Hunchback gradient is secondarily Caudal rengthened by the transcription of 5 Bicoid protein Pumilio the hunchback gene in the anterior nu- 8 Hunchback clei(since Bicoid acts as a transcription Nanos factor to activate hunchback transcrip protein tion).(C) Parallel interactions whereby Anterior Posterior translational gene regulation establishes the anterior-posterior patterning of the I Smibert195 Hunchback:母体mRNA在卵中均匀分布,受精后前区高浓度的 Bicoid蛋白 激活合子 hunchback基因的表达,从而帮助形成 hunchback蛋白浓度梯度 Caudal:母体mRNA在卵中均匀分布,受精后 bicoid蛋白抑制其在前区 的表达,因而 Caudal蛋白形成类似于 nanos的浓度梯度
Developmental Biology A－P轴线形成模式 Hunchback：母体mRNA在卵中均匀分布，受精后前区高浓度的Bicoid蛋白 激活合子hunchback基因的表达，从而帮助形成hunchback蛋白浓度梯度。 Caudal: 母体mRNA在卵中均匀分布，受精后bicoid蛋白抑制其在前区 的表达，因而Caudal蛋白形成类似于nanos的浓度梯度