Development

The three germ layers

The neural [blank_start]plate[blank_end] buckles at its midline to form the neural [blank_start]groove[blank_end] which folds and forms the neural [blank_start]tube[blank_end].

Folding of the neural plate. Name the two hinge points

The neural tube lies over the [blank_start]notochord[blank_end].

Drag and drop

Secondary neurolation refers to the development of [blank_start]posterior[blank_end] parts. Tubes from both primary and secondary neurulation [blank_start]eventually connect[blank_end].

BMP: [blank_start]Bone morphogenetic proteins[blank_end] FGF: [blank_start]Fibroplast growth factors[blank_end]

BMP4 signal induces [blank_start]epidermal[blank_end] differentiation. [blank_start]Inhibition[blank_end] of BMP is necessary to allow neural development. These processes are combined with signalling from [blank_start]FGF[blank_end].

Sonic hedgehog is secreted by the [blank_start]notochord[blank_end] and the [blank_start]floor[blank_end] plate.

Signals from the notochord induce the [blank_start]floor plate[blank_end] which induces [blank_start]ventral[blank_end] neurons. Signals from ectoderm induce the [blank_start]roof plate[blank_end] which induces [blank_start]dorsal[blank_end] neurons.

Differences in the concentration of sonic hedgehog (a single protein) can determine the fate of multiple neuronal classes in the [blank_start]ventral[blank_end] part of the neural tube. In a first step a ventral-to-dorsal Shh gradient [blank_start]activates and represses[blank_end] different transcription factors. These [blank_start]repress[blank_end] each other's expression to confer cell identity to progenitor cells unambiguously. Five cardinal progenitor domains are established: Four types of [blank_start]interneurons[blank_end] (V0 - V3) and [blank_start]motor neurons[blank_end].

The dorsal neural tube is patterned by [blank_start]BMP[blank_end] and dorsalin.

Inhibition of [blank_start]Wnt[blank_end] activity is required for the formation of rostral CNS structure, such as the forebrain. This is done via [blank_start]frzb[blank_end].

Which transcription factors are expressed at the midbrain-hindbrain boundary? Top of the picture is anterior (rostral).

Inductive influences

Overexpression of Gbx2 shifts the midbrain-hindbrain boundary [blank_start]anteriorly[blank_end].

Cells form the zona limitans intrathalamica secrete [blank_start]Shh[blank_end] which gives rise to the nuclei of the thalamus.

The functional and morphological segments of the hindbrain are called [blank_start]rhombomeres[blank_end]. There are [blank_start]eight[blank_end] of them (write digit).

The major class of genes that specifies motor neuron subtypes in the hindbrain is the [blank_start]Hox[blank_end] gene family. Their transcription is incuded or repressed by a gradient of [blank_start]retinoic[blank_end] acid.

[blank_start]Neural progenitors[blank_end] can divide symmetrically to two differentiated cells or two more progenitor cells. Or they can divide asymmetrically to one differentiated cell and one progenitor cell.

Delta: [blank_start]Ligand[blank_end] Notch: [blank_start]Receptor[blank_end]

Neurogenesis is the process by which a multitude of [blank_start]postmitotic[blank_end] neurons are generated from [blank_start]relatitvely few[blank_end] neural stem cells / progenitors in the neural [blank_start]epithelium[blank_end]. Neural stem cells are self-renewing and [blank_start]multipotent[blank_end].

Neurogenesis needs to balance the [blank_start]proliferation[blank_end] of more stem cells and the commitment to [blank_start]differentiation[blank_end] into neurons or glia cells.

Neuroblast ---[blank_start]asymmetric[blank_end]---> [blank_start]One neuroblast[blank_end] and [blank_start]one Ganglion Mother Cell[blank_end] ---[blank_start]symmetric[blank_end]---> [blank_start]Two neurons/glia cells or one each[blank_end]

Proneural genes give each cell in a group (proneural [blank_start]cluster[blank_end]) [blank_start]the same[blank_end] competence to become a proneuroblast. [blank_start]Lateral[blank_end] inhibition by delta-notch and a [blank_start]basic helix-loop-helix[blank_end] transcriptional cascade: More Delta in one cell [blank_start]enhances[blank_end] transcription of suppressor of hairless. Suppressor of hairless [blank_start]increases[blank_end] transcription of enhancer of split. Enhancer of split [blank_start]represses[blank_end] achaete-scute. Achaete-scute would increases expression of Delta but now does not. Therefore no Notch signalling in the original cell.

Proneural genes...

In [blank_start]insects[blank_end], the neurogenic pathway specifies neuroblasts, in [blank_start]vertebrates[blank_end] neurons are directly specified

Neuron production in the neural tube is related to changes in division pattern over time: symmetric versus asymmetric divisions.

In the neural tube: [blank_start]Apical[blank_end] stem cells at the [blank_start]ventricle[blank_end] [blank_start]proliferate[blank_end]. [blank_start]Basal[blank_end] cells at the [blank_start]pia[blank_end] [blank_start]differentiate[blank_end].

One important mechanism in the asymmetric divison of neuroblasts is the distribution of the protein [blank_start]numb[blank_end] which suppresses Notch signalling. After cell division only the [blank_start]GMC[blank_end] (GMC or neuroblast) will contain [blank_start]numb[blank_end].

Neurogenesis: 1) [blank_start]Subventricular zone[blank_end] of the striatum. The neuroblasts migrate to the [blank_start]olfactory bulb[blank_end] via the [blank_start]rostral migratory stream[blank_end]. 2) [blank_start]Dentate gyrus[blank_end] of the hippocampus. Controversial in adult humans.

In the subventricular zone [blank_start]stem cell niche cells[blank_end] regulate whether stem cells proliferate or divide [blank_start]asymmetrically[blank_end] (with one differentiating daughter cell) . This mechanism is regulated by [blank_start]signals from the blood vessels[blank_end].

Characteristics that have to be specified during cell development

Regional complexity of different neurons is achieved by

The growth cone is

The three main domains of the growth cone

Filopodia

Filopodia sense long-range cues [blank_start]chemically[blank_end] and short-range cues [blank_start]through contact[blank_end].

The reaction of filopodia to intracellular regulatory proteins (attraction or repulsion)

A good example for intracellular regulatory proteins that guide the growth of axons and can be both attracting and repelling are [blank_start]Netrins[blank_end]. They occur in particular at the [blank_start]floor plate[blank_end] of the neural tube and filopodia can have different receptors for them.

Retinal ganglion axons from the posterior (temporal) hemiretina project into the [blank_start]anterior[blank_end] developing tectum. Conversely, axons from the anterior (nasal) hemiretina project into the [blank_start]posterior[blank_end] tectum. Axons from explants of posterior retina row [blank_start]only on fragments[blank_end] [blank_start]from anterior tectal membrane[blank_end] while axons from anterior retina grow [blank_start]on both[blank_end] [blank_start]anterior and posterior tectal membrane[blank_end].

Gradients of [blank_start]Eph[blank_end] receptors and [blank_start]Ephrin[blank_end] ligands are responsible for the retinotopic organization of the tectum. Their cues are [blank_start]inhibitory / repelling[blank_end].

Every vertebrate brain has the same regions and only the nuclei are different.

The CNS forms from cells located on the dorsal side of the [blank_start]animal[blank_end] cap of the [blank_start]gastrula[blank_end] embryo.

Three BMP inhibitors (alphabetic): [blank_start]Chordin[blank_end] [blank_start]Follistatin[blank_end] [blank_start]Noggin[blank_end]

For neural induction a combination of [blank_start]BMP[blank_end] and [blank_start]FGF[blank_end] signalling is needed. The inhibition of [blank_start]BMP[blank_end] leads to a loss of inhibition of [blank_start]Zic1[blank_end] expression and [blank_start]FGF[blank_end] signalling induces [blank_start]Zic3[blank_end] expression. Zic1 and Zic3 are transcription factors.

In secondary neurolation the [blank_start]medullary[blank_end] cord condenses and later forms cavities. These cavities merge to a single tube.

In normal development [blank_start]N-cadherin[blank_end] is seen in the neural plate while [blank_start]E-cadherin[blank_end] is seen on the epidermis.

Failure of the closure of the neural tube can lead to [blank_start]anencephaly[blank_end] or [blank_start]spina bifida[blank_end] (alphabetic).

Sensory neurons are formed from [blank_start]neural crest[blank_end] cells.

The Shh pathway: Shh [blank_start]inhibits[blank_end] [blank_start]patched[blank_end] protein which [blank_start]inhibits[blank_end] [blank_start]smoothened[blank_end] protein which [blank_start]induces[blank_end] Gli/Ci [blank_start]activators[blank_end]. With Shh there are Gli/Ci [blank_start]activators[blank_end] and without Shh there are Gli/Ci [blank_start]repressors[blank_end].

The [blank_start]archenteron[blank_end] roof is responsible for [blank_start]anterior[blank_end] patterns. If it is transplanted to different locations of the early gastrula [blank_start]two heads emerge[blank_end].

One receptor for Wnt is [blank_start]frizzled[blank_end]. Wnt is inhibited by [blank_start]frzb[blank_end].

The forebrain is patterned by [blank_start]absence[blank_end] of Wnt activity. [blank_start]Increasing[blank_end] Wnt concentration specifies more caudal CNS domains.

Rotation of the midbrain-hindbrain boundary induces an additional [blank_start]organizer[blank_end] and the development of duplicate [blank_start]mdibrain[blank_end] structures.

The midbrain-hindbrain boundary

Retinoic acid is responsible for the expression of [blank_start]Hox[blank_end] genes and [blank_start]posterior[blank_end] patterning. Its concentration increases from [blank_start]anterior to posterior[blank_end].

A lack of Notch activity would lead to [blank_start]more[blank_end] neurons.

Stem cells proliferate at the [blank_start]ventricle[blank_end], differentiate a bit more basal and eventually migrate to the [blank_start]marginal[blank_end] layer.

Stem cells are proliferating [blank_start]very slowly[blank_end] while progenitors proliferate [blank_start]much faster[blank_end].

[blank_start]Microtubules[blank_end] act as transport pathways for cargo to the central core of the growth cone.

Three regional organizes (from anterior to posterior): [blank_start]Anterior neural border[blank_end] (ANB) [blank_start]Zonal imitans intrathalamica[blank_end] (ZLI) [blank_start]Midbrain-hindbrain boundary[blank_end] (MHB)

Neuroblasts and [blank_start]Ganglion Mother Cells[blank_end] are only existent in insects. In vertebrates the precursors of neurons and glia cells are called [blank_start]Radial Glial Cells[blank_end].