To reviewer A + editor
The reviewer has made a number of sensible points for which I am grateful, and I have amended the article as detailed below.
1: Definition of morphogenesis I have clarified the basic definition and used it consistently
2: Illustrations Fig. 1. I have improved the caption Fig. 2. The purpose of this picture is to show the participating cell types and I have clarified the caption Fig. 3. While the reviewer is technically correct in saying that branching involves an initial cavitation step, most people would not fuss over this, particularly in a WIKI article which has to be terse. I have slightly amended the caption
3: lack of discussion of mechanisms The article is not meant to include these and there is now a strong and early pointer to Jamie Davies' article on this
Other points 1: I have pointed out that the morphogenesis of unicellular organisms is not covered here 2: The relationship of morphogenesis to patterning and timing has now been clarified 3: I have rewritten the sentence on growth, apoptosis etc
4: I have spelt out that some morphogenetic events are to be viewed as more complicated than others in that they require the employment of more mechanisms.
5: The section entitled "Morphogenesis is important" is included to draw the reader's eye to the reasons why this topic matters in the wider biological context, but I agree that the phrase is unduly prominent and it is now less so
6: Are blood vessels 2D or 3D - the answer is of course both (depending on the choice of coordinate system). To clarify this, I have emphasised the sheet aspect of epithelia and rewritten the paragraph
7: I have corrected spelling mistakes and americanized the words
I have taken the opportunity of coming back to this article after some months to sharpen some of the layout and text
I have made changes directly to the article. I am, however, worried about fig 2 and I cannot make changes myself. There are two problems - the simplest one is that the fluorescent labels should be identified (which molecules are being detected). The other is that the upper right red object looks much more epithelial than mesenchymal, and seems to be inside the larger epithelial structure. Has the plane of section caught the moment of branching, or is something else going on? Would it not be simpler to use a more standard image to show what is intended to be shown?
March 31: Reviewer A does not see any modifications of the article that address the concerns.
An article of Dr Jonathan Bard discusses morphogenesis. Unfortunately this article has several major problems that need to be resolved prior to acceptance of the article.
First of all, there is no clear statement that defines the term morphogenesis in the article; there are several descriptions of morphogenesis in the article that are not exactly the same:
Morphogenesis means the generation form: the word is applied most often to biology, where it means the generation of biological form in animal and plant embryos (and also in complex single-cell organisms such as Acetabularia).
Morphogenesis is one of the four key interrelated processes that characterize all of development.
Morphogenesis The processes that generate tissue shape; these include proliferation and apoptosis as well as shape change.
Morphogenesis is a dynamic process driven by a limited number of molecular mechanisms involving the cell surface (e.g. adhesion molecules) and the cytoskeleton. Morphogenesis therefore deals with straightforward questions such as how cells, tissues, organs and organisms change their shape (or become different).
This leaves an impression that the author does not really know what morphogenesis is. Perhaps it is better to combine all these explanations in one sentence.
Second, some of the illustrations are very good but their purpose is not clear. Fig.1. It is not clear how a section through an early mouse kidney (that does not really illustrate change of the shape) can help to understand what morphogenesis is.
Fig. 2. ‘confocal micrograph of an early (E13) mouse kidney’ Is not really a clear example either. The figure legend points out the formation of lumen and basement lamina that makes one think that these two are important attributes of morphogenesis. Morphogenesis is dynamic process so as an example the author should show a sequence of pictures representing shape changes during morphogenesis. Fig. 3h. Branching morphogenesis is not a basic mode of morphogenetic movement. It includes at least two other “basic” modes from Fig. 3, such as invagination and cavitation.
Third, there is no clear discussion of mechanisms of morphogenesis in the article. I think that mechanisms of morphogenesis should be clearly named, clearly explained and supplied with appropriate connections to corresponding articles within scholarpedia or with good examples.
For example: Molecular mechanism: gene expression, mutations and etc. Chemical mechanism: morphogenetic gradients, growth factor signaling, chemotaxis. Mechanical mechanism: cell adhesion, adhesion gradients, applied mechanical strength (cell matrix, cytoskeleton), and etc. Cell signaling: cell-cell interaction (gap junction, ephs and ephrins, synapses?); cell extracellular matrix signaling and etc.
I. The article needs to explain the difference between morphogenesis of unicellular multicellular organisms and plants or give a suitable general description of morphogenesis for all these groups of organisms (at least common between unicellular and multicellular organisms).
II. Author writes: Morphogenesis is one of the four key interrelated processes that characterize all of development: 1.Patterning 2. Cell differentiation 3. Morphogenesis The processes that generate tissue shape; these include proliferation and apoptosis as well as shape change 4. Regulation of timing. Thus, morphogenesis is one of the four processes that characterize the development. However, the explanation of the term morphogenesis here states that morphogenesis is a process that generates tissue shape. In that case what about patterning and cell differentiation? These processes clearly generate tissue shape change, so according to the description of morphogenesis they should be parts of morphogenesis?
III. Author has to find a clear place for cell proliferation and cell apoptosis. Examples: “Tissue organisation arises from cells exhibiting well-defined morphogenetic behaviours (e.g. movement and shape change) as well as differential growth and apoptosis (programmed cell death). “ In this sentence apoptosis is a process that exists separately from morphogenesis. “Morphogenesis The processes that generate tissue shape; these include proliferation and apoptosis as well as shape change”. In this sentence apoptosis is included in morphogenesis.
IV. Author writes: Morphogenesis therefore deals with straightforward questions such as: how do epithelial ducts branch in glands? (Fig.2), how do nerves migrate to and recognise their targets?, how do mesenchymal cells come together to form pre-muscle and pre-bone condensations?, how do tendons link to the appropriate bones?, and how do cells change their shapes? Morphogenesis also covers more complicated questions such as: how are bones shaped, and how does the simple heart tube reorganise itself and its associated blood vessels to produce the 4-chambered heart of mammals and birds? Why the questions how bones shaped or 4-chambered heart develops are more complicated then all “straightforward” questions, such as nerve migration or formation of mesenchymal condensations?
V. Why is the paragraph “Morphogenesis is important” needed? This statement should be clear from the first paragraph without explanation.
VI. In the paragraph that begins The participating cells… Blood vessels and glands (in the paragraph “controlled growth (e.g. the extension and branching of ducts)”, “Endothelia form the tubes of the vascular system”) many other authors consider these as 3D structures.
VII. There are some misspellings that need to be taken care of.
Conclusion: This article needs to be changed substantially to clarify all points. May 7, 2008 I am accepting article now, however, as I suggested previously, the mechanisms of morphogenesis at least should be mentioned in a separate paragraph with the links to appropriate articles.
For example: Molecular mechanisms: gene expression, mutations and etc. Chemical mechanisms: morphogenetic gradients, growth factor signaling, chemotaxis. Mechanical mechanisms: cell adhesion, adhesion gradients, applied mechanical strength (cell matrix, cytoskeleton), and etc. Cell signaling: cell-cell interaction (gap junction, ephs and ephrins, synapses?); cell extracellular matrix signaling and etc.
User 4: Etymology
Etymology from Greek μορφο- form/shape, and γένεσις generation.
This is a very minor change to be placed near the first time morphogenesis appears Elias